Female mosquitoes of several species require blood from warmblooded animals,including humans for the purpose of reproduction.In this process,several microbes residing in the salivary gland and midgut of mosquitoes als...Female mosquitoes of several species require blood from warmblooded animals,including humans for the purpose of reproduction.In this process,several microbes residing in the salivary gland and midgut of mosquitoes also get transferred from one human individual to the other–a traditional model by which many vector-borne diseases(VBDs)get transmitted in the population through mosquitoes belonging to Anopheles,Aedes,Culex and other genera.展开更多
Vector-borne diseases are highly sensitive to environment and to environmental changes. Rift Valley Fever (RFV) is a mosquito-borne zootic virus associated with severe diseases in human beings and economic consequence...Vector-borne diseases are highly sensitive to environment and to environmental changes. Rift Valley Fever (RFV) is a mosquito-borne zootic virus associated with severe diseases in human beings and economic consequences to livestock sector. Animal and human movements have a fundamental impact on RVF transmission. In recent years, there has been a growing interest in the use of mathematics and agent based models to represent and analyze the dynamic of RFV transmission. However, no previous study has taken into consideration animal herds’ mobility and precipitation factors to understand the disease spread. This limitation underlines the necessity to use computational model approach based on multi-agent system in the study of vector-borne diseases transmission and diffusion. In this paper, a multi-agent system combining conceptual model expressiveness is used to study animal herds’ mobility and the precipitation parameter impact on the Rift Valley Fever outbreak in Ferlo Barkedji in Northern Senegal. Simulation scenarios with various parameters, including rain quality, hosts, vectors, camp dispersal around ponds, etc., are unrolled. The different results we have obtained show that the evolution of the number of infected hosts and infected vectors depend on the degree of animal herds’ mobility and on precipitations. Our model provides a framework that permits predicting the spread of the disease associated with the mobility of animal herds.展开更多
Background: Social determinants of health (SDOH) significantly influence diseases with environmental components, like vector-borne parasitic diseases. This study aims to examine how these factors influence vector-born...Background: Social determinants of health (SDOH) significantly influence diseases with environmental components, like vector-borne parasitic diseases. This study aims to examine how these factors influence vector-borne parasitic diseases (VBPDs) transmission in Chad and provide recommendations for policy improvements. Methods: The study adopts the WHO Conceptual Framework of SDOH to compare two regions in Southern Chad: Kouh-Est, which has an ongoing vector control program, and Grand-Sido, which lacks such a program. The study includes both nomadic and sedentary populations to provide a comprehensive understanding of the SDOH influencing VBPDs. Households were randomly selected. Data on sociodemographic characteristics, literacy, knowledge of VBPDs and protective measures, and access to education and health facilities were collected. Results: A total of 202 households from 17 villages, including 820 participants, were surveyed. Agriculture, livestock, and fishing were the main occupations, involving 84.1% of participants. Literacy was low, with 36.7% non-educated, 47.7% completing primary school, 14.5% secondary school, and only 0.3% reaching tertiary education. Most villages lacked schools beyond the primary level, and nomadic populations were significantly less educated than sedentary ones (p Conclusion: Educational deficiencies, lack of protective measures against vectors, inadequate healthcare resources, and lifestyle conditions aggravated by poor road infrastructure, limited transportation, and economic constraints contribute to worsened VBPDs outcomes in these rural populations. Addressing these systemic issues in the surveyed communities is essential for improving health equity and VBPDs outcomes in these regions specifically and in similar populations settings more broadly.展开更多
Introduction:Vector-borne diseases(VBDs)represent a significant category of infectious diseases.Analyzing the epidemiological characteristics of VBDs in China,including their temporal and spatial distributions,provide...Introduction:Vector-borne diseases(VBDs)represent a significant category of infectious diseases.Analyzing the epidemiological characteristics of VBDs in China,including their temporal and spatial distributions,provides essential evidence for developing effective prevention and control strategies.Methods:Data for 14 types of VBDs from 2005 to 2024 were obtained from the China National Infectious Disease Surveillance System.These diseases were categorized as mosquito-borne,tick-borne,rodent-borne,and other VBDs.Using the Mann-Kendall trend test,we analyzed demographic characteristics,spatial distribution,temporal trends,and seasonal patterns of notified cases over the 20-year period.Results:From 2005 to 2024,a total of 1,129,736 VBD cases were reported in China.Scrub typhus(28.17%),malaria(20.8%),hemorrhagic fever with renal syndrome(HFRS,18.4%),dengue(12.61%),and schistosomiasis(8.42%)collectively accounted for 88.4%of all cases.Over a 20-year period,mosquitoborne and rodent-borne diseases indicated significant declining trends(P<0.05),while tick-borne and other VBDs demonstrated significant increasing trends(P<0.05).Dengue,scrub typhus,and severe fever with thrombocytopenia syndrome(SFTS)expanded geographically,with annual increases of 10.89,12.37,and 7.07 reporting cities,respectively.Although diseases such as plague,malaria,and schistosomiasis have been effectively controlled,the incidence of scrub typhus,dengue,HFRS,and SFTS has remained high in recent years.Conclusions:The burden of VBDs in China remains substantial,with an increasing trend observed over the past 5 years.The rising incidence and geographic expansion of scrub typhus,dengue,and SFTS warrant particular attention from public health authorities.展开更多
Background:Diseases transmitted to humans by vectors account for 17%of all infectious diseases and remain significant public health problems.Through the years,great strides have been taken towards combatting vectorbor...Background:Diseases transmitted to humans by vectors account for 17%of all infectious diseases and remain significant public health problems.Through the years,great strides have been taken towards combatting vectorborne diseases(VBDs),most notably through large scale and coordinated control programmes,which have contributed to the decline of the global mortality attributed to VBDs.However,with environmental changes,including climate change,the impact on VBDs is anticipated to be significant,in terms of VBD-related hazards,vulnerabilities and exposure.While there is growing awareness on the vulnerability of the African continent to VBDs in the context of climate change,there is still a paucity of research being undertaken in this area,and impeding the formulation of evidence-based health policy change.Main body:One way in which the gap in knowledge and evidence can be filled is for donor institutions to support research in this area.The collaboration between the WHO Special Programme for Research and Training in Tropical Diseases(TDR)and the International Centre for Research and Development(IDRC)builds on more than 10 years of partnership in research capacity-building in the field of tropical diseases.From this partnership was born yet another research initiative on VBDs and the impact of climate change in the Sahel and sub-Saharan Africa.This paper lists the projects supported under this research initiative and provides a brief on some of the policy and good practice recommendations emerging from the ongoing implementation of the research projects.Conclusion:Data generated from the research initiative are expected to be uptaken by stakeholders(including communities,policy makers,public health practitioners and other relevant partners)to contribute to a better understanding of the impacts of social,environmental and climate change on VBDs(i.e.the nature of the hazard,vulnerabilities,exposure),and improve the ability of African countries to adapt to and reduce the effects of these changes in ways that benefit their most vulnerable populations.展开更多
This paper highlights the critical importance of evidence on vector-borne diseases(VBD)prevention and control interventions in urban settings when assessing current and future needs,with a view to setting policy prior...This paper highlights the critical importance of evidence on vector-borne diseases(VBD)prevention and control interventions in urban settings when assessing current and future needs,with a view to setting policy priorities that promote inclusive and equitable urban health services.Research should produce knowledge about policies and interventions that are intended to control and prevent VBDs at the population level and to reduce inequities.Such interventions include policy,program,and resource distribution approaches that address the social determinants of health and exert influence at organizational and system levels.展开更多
Background:Climate-based disease forecasting has been proposed as a potential tool in climate change adaptation for the health sector.Here we explore the relevance of climate data,drivers and predictions for vector-bo...Background:Climate-based disease forecasting has been proposed as a potential tool in climate change adaptation for the health sector.Here we explore the relevance of climate data,drivers and predictions for vector-borne disease control efforts in Africa.Methods:Using data from a number of sources we explore rainfall and temperature across the African continent,from seasonality to variability at annual,multi-decadal and timescales consistent with climate change.We give particular attention to three regions defined as WHO-TDR study zones in Western,Eastern and Southern Africa.Our analyses include 1)time scale decomposition to establish the relative importance of year-to-year,decadal and long term trends in rainfall and temperature;2)the impact of the El Niño Southern Oscillation(ENSO)on rainfall and temperature at the Pan African scale;3)the impact of ENSO on the climate of Tanzania using high resolution climate products and 4)the potential predictability of the climate in different regions and seasons using Generalized Relative Operating Characteristics.We use these analyses to review the relevance of climate forecasts for applications in vector borne disease control across the continent.Results:Timescale decomposition revealed long term warming in all three regions of Africa-at the level of 0.1-0.3°C per decade.Decadal variations in rainfall were apparent in all regions and particularly pronounced in the Sahel and during the East African long rains(March-May).Year-to-year variability in both rainfall and temperature,in part associated with ENSO,were the dominant signal for climate variations on any timescale.Observed climate data and seasonal climate forecasts were identified as the most relevant sources of climate information for use in early warning systems for vector-borne diseases but the latter varied in skill by region and season.Conclusions:Adaptation to the vector-borne disease risks of climate variability and change is a priority for government and civil society in African countries.Understanding rainfall and temperature variations and trends at multiple timescales and their potential predictability is a necessary first step in the incorporation of relevant climate information into vector-borne disease control decision-making.展开更多
Background:The control of vector-borne diseases(VBD)is one of the greatest challenges on the global health agenda.Rapid and uncontrolled urbanization has heightened the interest in addressing these challenges through ...Background:The control of vector-borne diseases(VBD)is one of the greatest challenges on the global health agenda.Rapid and uncontrolled urbanization has heightened the interest in addressing these challenges through an integrated vector management(IVM)approach.The aim was to identify components related to impacts,economic evaluation,and sustainability that might contribute to this integrated approach to VBD prevention.Main body:We conducted a scoping review of available literature(2000-2016)using PubMed,Web of Science,Cochrane,CINAHL,Econlit,LILACS,Global Health Database,Scopus,and Embase,as well as Tropical Diseases Bulletin,WHOLIS,WHO Pesticide Evaluation Scheme,and Google Scholar.MeSH terms and free-text terms were used.A data extraction form was used,including TIDieR and ASTAIRE.MMAT and CHEERS were used to evaluate quality.Of the 42 documents reviewed,30 were focused on dengue,eight on malaria,and two on leishmaniasis.More than a half of the studies were conducted in the Americas.Half used a quantitative descriptive approach(n=21),followed by cluster randomized controlled trials(n=11).Regarding impacts,outcomes were:a)use of measures for vector control;b)vector control;c)health measures;and d)social measures.IVM reduced breeding sites,the entomology index,and parasite rates.Results were heterogeneous,with variable magnitudes,but in all cases were favourable to the intervention.Evidence of IVM impacts on health outcomes was very limited but showed reduced incidence.Social outcomes were improved abilities and capacities,empowerment,and community knowledge.Regarding economic evaluation,only four studies performed an economic analysis,and intervention benefits outweighed costs.Costeffectiveness was dependent on illness incidence.The results provided key elements to analyze sustainability in terms of three dimensions(social,economic,and environmental),emphasizing the implementation of a community-focused eco-bio-social approach.Conclusions:IVM has an impact on reducing vector breeding sites and the entomology index,but evidence of impacts on health outcomes is limited.Social outcomes are improved abilities and capacities,empowerment,and community knowledge.Economic evaluations are scarce,and cost-effectiveness is dependent on illness incidence.Community capacity building is the main component of sustainability,together with collaboration,institutionalization,and routinization of activities.Findings indicate a great heterogeneity in the interventions and highlight the need for characterizing interventions rigorously to facilitate transferability.展开更多
The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of th...The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.展开更多
We look at the link between climate change and vector-borne diseases in low-and middle-income countries in Africa.The large endemicity and escalating threat of diseases such as malaria and arboviral diseases,intensifi...We look at the link between climate change and vector-borne diseases in low-and middle-income countries in Africa.The large endemicity and escalating threat of diseases such as malaria and arboviral diseases,intensified by climate change,disproportionately affects vulnerable communities globally.We highlight the urgency of prioritizing research and development,advocating for robust scientific inquiry to promote adaptation strategies,and the vital role that the next generation of African research leaders will play in addressing these challenges.Despite significant challenges such as funding shortages within countries,various pan-African-oriented funding bodies such as the African Academy of Sciences,the Africa Research Excellence Fund,the Wellcome Trust,the U.S.National Institutes of Health,and the Bill and Melinda Gates Foundation as well as initiatives such as the African Research Initiative for Scientific Excellence and the Pan-African Mosquito Control Association,have empowered(or are empowering)these researchers by supporting capacity building activities,including continental and global networking,skill development,mentoring,and African-led research.This article underscores the urgency of increased national investment in research,proposing the establishment of research government agencies to drive evidence-based interventions.Collaboration between governments and scientific communities,sustained by pan-African funding bodies,is crucial.Through these efforts,African nations are likely to enhance the resilience and adaptive capacity of their systems and communities by navigating these challenges effectively,fostering scientific excellence and implementing transformative solutions against climate-sensitive vector-borne diseases.展开更多
Background:In 2015,following a call for proposals from the Special Programme for Research and Training in Tropical Diseases(TDR),six scoping reviews on the prevention and control of vector-borne diseases in urban area...Background:In 2015,following a call for proposals from the Special Programme for Research and Training in Tropical Diseases(TDR),six scoping reviews on the prevention and control of vector-borne diseases in urban areas were conducted.Those reviews provided a clear picture of the available knowledge and highlighted knowledge gaps,as well as needs and opportunities for future research.Based on the research findings of the scoping reviews,a concept mapping exercise was undertaken to produce a list of priority research needs to be addressed.Methods:Members of the six research teams responsible for the“VEctor boRne DiseAses Scoping reviews”(VERDAS)consortium’s scoping reviews met for 2 days with decision-makers from Colombia,Brazil,Peru,Pan-American Health Organization,and World Health Organization.A total of 11 researchers and seven decision-makers(from ministries of health,city and regional vector control departments,and vector control programs)completed the concept mapping,answering the question:“In view of the knowledge synthesis and your own expertise,what do we still need to know about vector-borne diseases and other infectious diseases of poverty in urban areas?”Participants rated each statement on two scales from 1 to 5,one relative to‘priority’and the other to‘policy relevance’,and grouped statements into clusters based on their own individual criteria and expertise.Results:The final map consisted of 12 clusters.Participants considered those entitled“Equity”,“Technology”,and“Surveillance”to have the highest priority.The cluster considered the most important concerns equity issues,confirming that these issues are rarely addressed in research on vector-borne diseases.On the other hand,the“Population mobility”and“Collaboration”clusters were considered to be the lowest priority but remained identified by participants as research priorities.The average policy relevance scores for each of the 12 clusters were roughly the same as the priority scores for all clusters.Some issues were not addressed during the brain-storming.This is the case for governance and for access and quality of care.Conclusions:Based on this work,and adopting a participatory approach,the concept mapping exercise conducted collaboratively with researchers from these teams and high-level decision-makers identified research themes for which studies should be carried out as a priority.展开更多
Peroxisome proliferator-activated receptor alpha is a member of the nuclear hormone receptor superfamily and functions as a transcription factor involved in regulating cellular metabolism.Previous studies have shown t...Peroxisome proliferator-activated receptor alpha is a member of the nuclear hormone receptor superfamily and functions as a transcription factor involved in regulating cellular metabolism.Previous studies have shown that PPARαplays a key role in the onset and progression of neurodegenerative diseases.Consequently,peroxisome proliferator-activated receptor alpha agonists have garnered increasing attention as potential treatments for neurological disorders.This review aims to clarify the research progress regarding peroxisome proliferator-activated receptor alpha in nervous system diseases.Peroxisome proliferator-activated receptor alpha is present in all cell types within adult mouse and adult neural tissues.Although it is conventionally believed to be primarily localized in the nucleus,its function may be regulated by a dynamic balance between cytoplasmic and nuclear shuttling.Both endogenous and exogenous peroxisome proliferator-activated receptor alpha agonists bind to the peroxisome proliferator-activated response element to exert their biological effects.Peroxisome proliferator-activated receptor alpha plays a significant therapeutic role in neurodegenerative diseases.For instance,peroxisome proliferator-activated receptor alpha agonist gemfibrozil has been shown to reduce levels of soluble and insoluble amyloid-beta in the hippocampus of Alzheimer's disease mouse models through the autophagy-lysosomal pathway.Additionally,peroxisome proliferator-activated receptor alpha is essential for the normal development and functional maintenance of the substantia nigra,and it can mitigate motor dysfunction in Parkinson's disease mouse models.Furthermore,peroxisome proliferator-activated receptor alpha has been found to reduce neuroinflammation and oxidative stress in various neurological diseases.In summary,peroxisome proliferator-activated receptor alpha plays a crucial role in the onset and progression of multiple nervous system diseases,and peroxisome proliferator-activated receptor alpha agonists hold promise as new therapeutic agents for the treatment of neurodegenerative diseases,providing new options for patient care.展开更多
Chemical exchange saturation transfer magnetic resonance imaging is an advanced imaging technique that enables the detection of compounds at low concentrations with high sensitivity and spatial resolution and has been...Chemical exchange saturation transfer magnetic resonance imaging is an advanced imaging technique that enables the detection of compounds at low concentrations with high sensitivity and spatial resolution and has been extensively studied for diagnosing malignancy and stroke.In recent years,the emerging exploration of chemical exchange saturation transfer magnetic resonance imaging for detecting pathological changes in neurodegenerative diseases has opened up new possibilities for early detection and repetitive scans without ionizing radiation.This review serves as an overview of chemical exchange saturation transfer magnetic resonance imaging with detailed information on contrast mechanisms and processing methods and summarizes recent developments in both clinical and preclinical studies of chemical exchange saturation transfer magnetic resonance imaging for Alzheimer’s disease,Parkinson’s disease,multiple sclerosis,and Huntington’s disease.A comprehensive literature search was conducted using databases such as PubMed and Google Scholar,focusing on peer-reviewed articles from the past 15 years relevant to clinical and preclinical applications.The findings suggest that chemical exchange saturation transfer magnetic resonance imaging has the potential to detect molecular changes and altered metabolism,which may aid in early diagnosis and assessment of the severity of neurodegenerative diseases.Although promising results have been observed in selected clinical and preclinical trials,further validations are needed to evaluate their clinical value.When combined with other imaging modalities and advanced analytical methods,chemical exchange saturation transfer magnetic resonance imaging shows potential as an in vivo biomarker,enhancing the understanding of neuropathological mechanisms in neurodegenerative diseases.展开更多
Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions.They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute cour...Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions.They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute course contingent upon the site of damage.The main types include amyotrophic lateral sclerosis,progressive muscular atrophy,primary lateral sclerosis,and progressive bulbar palsy,the pathological processes of which are largely identical,with the main disparity lying in the location of the lesions.Amyotrophic lateral sclerosis is the representative condition in this group of diseases,while other types are its variants.Hence,this article mainly focuses on the advancements and challenges in drug research for amyotrophic lateral sclerosis but also briefly addresses several other important degenerative motor neuron diseases.Although the precise pathogenesis remains elusive,recent advancements have shed light on various theories,including gene mutation,excitatory amino acid toxicity,autoimmunology,and neurotrophic factors.The US Food and Drug Administration has approved four drugs for use in delaying the progression of amyotrophic lateral sclerosis:riluzole,edaravone,AMX0035,and tofersen,with the latter being the most recent to receive approval.However,following several phaseⅢtrials that failed to yield favorable outcomes,AMX0035 has been voluntarily withdrawn from both the US and Canadian markets.This article presents a comprehensive summary of drug trials primarily completed between January 1,2023,and June 30,2024,based on data sourced from clinicaltrials.gov.Among these trials,five are currently in phaseⅠ,seventeen are in phaseⅡ,and eleven are undergoing phaseⅢevaluation.Notably,24 clinical trials are now investigating potential disease-modifying therapy drugs,accounting for the majority of the drugs included in this review.Some promising drugs being investigated in preclinical studies,such as ATH-1105,are included in our analysis,and another review in frontiers in gene therapy and immunotherapy has demonstrated their therapeutic potential for motor neuron diseases.This article was written to be an overview of research trends and treatment prospects related to motor neuron disease drugs,with the aim of highlighting the latest potentialities for clinical therapy.展开更多
In recent years,exosomes have garnered extensive attention as therapeutic agents and early diagnostic markers in neurodegenerative disease research.Exosomes are small and can effectively cross the blood-brain barrier,...In recent years,exosomes have garnered extensive attention as therapeutic agents and early diagnostic markers in neurodegenerative disease research.Exosomes are small and can effectively cross the blood-brain barrier,allowing them to target deep brain lesions.Recent studies have demonstrated that exosomes derived from different cell types may exert therapeutic effects by regulating the expression of various inflammatory cytokines,mRNAs,and disease-related proteins,thereby halting the progression of neurodegenerative diseases and exhibiting beneficial effects.However,exosomes are composed of lipid bilayer membranes and lack the ability to recognize specific target cells.This limitation can lead to side effects and toxicity when they interact with non-specific cells.Growing evidence suggests that surface-modified exosomes have enhanced targeting capabilities and can be used as targeted drug-delivery vehicles that show promising results in the treatment of neurodegenerative diseases.In this review,we provide an up-to-date overview of existing research aimed at devising approaches to modify exosomes and elucidating their therapeutic potential in neurodegenerative diseases.Our findings indicate that exosomes can efficiently cross the blood-brain barrier to facilitate drug delivery and can also serve as early diagnostic markers for neurodegenerative diseases.We introduce the strategies being used to enhance exosome targeting,including genetic engineering,chemical modifications(both covalent,such as click chemistry and metabolic engineering,and non-covalent,such as polyvalent electrostatic and hydrophobic interactions,ligand-receptor binding,aptamer-based modifications,and the incorporation of CP05-anchored peptides),and nanomaterial modifications.Research into these strategies has confirmed that exosomes have significant therapeutic potential for neurodegenerative diseases.However,several challenges remain in the clinical application of exosomes.Improvements are needed in preparation,characterization,and optimization methods,as well as in reducing the adverse reactions associated with their use.Additionally,the range of applications and the safety of exosomes require further research and evaluation.展开更多
Myelination,the continuous ensheathment of neuronal axons,is a lifelong process in the nervous system that is essential for the precise,temporospatial conduction of action potentials between neurons.Myelin also provid...Myelination,the continuous ensheathment of neuronal axons,is a lifelong process in the nervous system that is essential for the precise,temporospatial conduction of action potentials between neurons.Myelin also provides intercellular metabolic support to axons.Even minor disruptions in the integrity of myelin can impair neural performance and increase susceptibility to neurological diseases.In fact,myelin degeneration is a well-known neuropathological condition that is associated with normal aging and several neurodegenerative diseases,including multiple sclerosis and Alzheimer’s disease.In the central nervous system,compact myelin sheaths are formed by fully mature oligodendrocytes.However,the entire oligodendrocyte lineage is susceptible to changes in the biological microenvironment and other risk factors that arise as the brain ages.In addition to their well-known role in action potential propagation,oligodendrocytes also provide intercellular metabolic support to axons by transferring energy metabolites and delivering exosomes.Therefore,myelin degeneration in the aging central nervous system is a significant contributor to the development of neurodegenerative diseases.Interventions that mitigate age-related myelin degeneration can improve neurological function in aging individuals.In this review,we investigate the changes in myelin that are associated with aging and their underlying mechanisms.We also discuss recent advances in understanding how myelin degeneration in the aging brain contributes to neurodegenerative diseases and explore the factors that can prevent,slow down,or even reverse age-related myelin degeneration.Future research will enhance our understanding of how reducing age-related myelin degeneration can be used as a therapeutic target for delaying or preventing neurodegenerative diseases.展开更多
With the gradual advancement of research methods and technologies,various biological processes have been identified as playing roles in the pathogenesis of neurodegenerative diseases.However,current descriptions of th...With the gradual advancement of research methods and technologies,various biological processes have been identified as playing roles in the pathogenesis of neurodegenerative diseases.However,current descriptions of these biological processes do not fully explain the onset,progression,and development of these conditions.Therefore,exploration of the pathogenesis of neurodegenerative diseases remains a valuable area of research.This review summarizes the potential common pathogeneses of Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,Huntington’s disease,frontotemporal lobar dementia,and Lewy body disease.Research findings have indicated that several common biological processes,including aging,genetic factors,progressive neuronal dysfunction,neuronal death and apoptosis,protein misfolding and aggregation,neuroinflammation,mitochondrial dysfunction,axonal transport defects,and gut microbiota dysbiosis,are involved in the pathogenesis of these six neurodegenerative diseases.Based on current information derived from diverse areas of research,these biological processes may form complex pathogenic networks that lead to distinctive types of neuronal death in neurodegenerative diseases.Furthermore,promoting the regeneration of damaged neurons may be achievable through the repair of affected neural cells if the underlying pathogenesis can be prevented or reversed.Hence,these potential common biological processes may represent only very small,limited elements within numerous intricate pathogenic networks associated with neurodegenerative diseases.In clinical treatment,interfering with any single biological process has proven insufficient to completely halt the progression of neurodegenerative diseases.Therefore,future research on the pathogenesis of neurodegenerative diseases should focus on uncovering the complex pathogenic networks,rather than isolating individual biological processes.Based on this,therapies that aim to block or reverse various targets involved in the potential pathogenic mechanisms of neurodegenerative diseases may be promising directions,as current treatment methods that focus on halting a single pathogenic factor have not achieved satisfactory efficacy.展开更多
For diverse neurodegenerative disorders,microglial cells are activated.Furthermore,dysfunctional and hyperactivated microglia initiate mitochondrial autophagy,oxidative stress,and pathological protein accumulation,end...For diverse neurodegenerative disorders,microglial cells are activated.Furthermore,dysfunctional and hyperactivated microglia initiate mitochondrial autophagy,oxidative stress,and pathological protein accumulation,ending with neuroinflammation that exacerbates damage to dopaminergic neurons and contributes significantly to the pathology of neurodegenerative disorder.Microglial overactivation is closely associated with the secretion of pro-inflammatory cytokines,the phagocytosis of injured neurons,and the modulation of neurotoxic environments.This review summarizes the role of microglia neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease,multiple sclerosis,multiple system atrophy,amyotrophic lateral sclerosis,frontotemporal dementia,progressive supranuclear palsy,cortical degeneration,Lewy body dementia,and Huntington's disease.It also discusses novel forms of cell death such as ferroptosis,cuproptosis,disulfidptosis,and parthanatos(poly(adenosine diphosphate ribose)polymerase 1-dependent cell death),as well as the impact of regulatory factors related to microglial inflammation on microglial activation and neuroinflammation.The aim is to identify potential targets for microglial cell therapy in neurodegenerative diseases.展开更多
Neurodegenerative diseases are a group of illnesses characterized by the gradual deterioration of the central nervous system,leading to a decline in patients'cognitive,motor,and emotional abilities.Neuroinflammati...Neurodegenerative diseases are a group of illnesses characterized by the gradual deterioration of the central nervous system,leading to a decline in patients'cognitive,motor,and emotional abilities.Neuroinflammation plays a significant role in the progression of these diseases.However,there is limited research on therapeutic approaches to specifically target neuroinflammation.The role of T lymphocytes,which are crucial mediators of the adaptive immune response,in neurodegenerative diseases has been increasingly recognized.This review focuses on the involvement of T lymphocytes in the neuroinflammation associated with neurodegenerative diseases.The pathogenesis of neurodegenerative diseases is complex,involving multiple mechanisms and pathways that contribute to the gradual degeneration of neurons,and T cells are a key component of these processes.One of the primary factors driving neuroinflammation in neurodegenerative diseases is the infiltration of T cells and other neuroimmune cells,including microglia,astrocytes,B cells,and natural killer cells.Different subsets of CD4~+T cells,such as Th1,Th2,Th17,and regulatory T cells,can differentiate into various cell types and perform distinct roles within the neuroinflammatory environment of neurodegenerative diseases.Additionally,CD8~+T cells,which can directly regulate immune responses and kill target cells,also play several important roles in neurodegenerative diseases.Clinical trials investigating targeted T cell therapies for neurodegenerative diseases have shown that,while some patients respond positively,others may not respond as well and may even experience adverse effects.Targeting T cells precisely is challenging due to the complexity of immune responses in the central nervous system,which can lead to undesirable side effects.However,with new insights into the pathophysiology of neurodegenerative diseases,there is hope for the establishment of a solid theoretical foundation upon which innovative treatment strategies that target T cells can be developed in the future.展开更多
The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cereb...The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.展开更多
文摘Female mosquitoes of several species require blood from warmblooded animals,including humans for the purpose of reproduction.In this process,several microbes residing in the salivary gland and midgut of mosquitoes also get transferred from one human individual to the other–a traditional model by which many vector-borne diseases(VBDs)get transmitted in the population through mosquitoes belonging to Anopheles,Aedes,Culex and other genera.
文摘Vector-borne diseases are highly sensitive to environment and to environmental changes. Rift Valley Fever (RFV) is a mosquito-borne zootic virus associated with severe diseases in human beings and economic consequences to livestock sector. Animal and human movements have a fundamental impact on RVF transmission. In recent years, there has been a growing interest in the use of mathematics and agent based models to represent and analyze the dynamic of RFV transmission. However, no previous study has taken into consideration animal herds’ mobility and precipitation factors to understand the disease spread. This limitation underlines the necessity to use computational model approach based on multi-agent system in the study of vector-borne diseases transmission and diffusion. In this paper, a multi-agent system combining conceptual model expressiveness is used to study animal herds’ mobility and the precipitation parameter impact on the Rift Valley Fever outbreak in Ferlo Barkedji in Northern Senegal. Simulation scenarios with various parameters, including rain quality, hosts, vectors, camp dispersal around ponds, etc., are unrolled. The different results we have obtained show that the evolution of the number of infected hosts and infected vectors depend on the degree of animal herds’ mobility and on precipitations. Our model provides a framework that permits predicting the spread of the disease associated with the mobility of animal herds.
文摘Background: Social determinants of health (SDOH) significantly influence diseases with environmental components, like vector-borne parasitic diseases. This study aims to examine how these factors influence vector-borne parasitic diseases (VBPDs) transmission in Chad and provide recommendations for policy improvements. Methods: The study adopts the WHO Conceptual Framework of SDOH to compare two regions in Southern Chad: Kouh-Est, which has an ongoing vector control program, and Grand-Sido, which lacks such a program. The study includes both nomadic and sedentary populations to provide a comprehensive understanding of the SDOH influencing VBPDs. Households were randomly selected. Data on sociodemographic characteristics, literacy, knowledge of VBPDs and protective measures, and access to education and health facilities were collected. Results: A total of 202 households from 17 villages, including 820 participants, were surveyed. Agriculture, livestock, and fishing were the main occupations, involving 84.1% of participants. Literacy was low, with 36.7% non-educated, 47.7% completing primary school, 14.5% secondary school, and only 0.3% reaching tertiary education. Most villages lacked schools beyond the primary level, and nomadic populations were significantly less educated than sedentary ones (p Conclusion: Educational deficiencies, lack of protective measures against vectors, inadequate healthcare resources, and lifestyle conditions aggravated by poor road infrastructure, limited transportation, and economic constraints contribute to worsened VBPDs outcomes in these rural populations. Addressing these systemic issues in the surveyed communities is essential for improving health equity and VBPDs outcomes in these regions specifically and in similar populations settings more broadly.
基金Supported by the consultancy project(2023-JB-12)from the Chinese Academy of Engineering(CAE)the Key Program of the National Natural Science Foundation of China(GRANT32090023).
文摘Introduction:Vector-borne diseases(VBDs)represent a significant category of infectious diseases.Analyzing the epidemiological characteristics of VBDs in China,including their temporal and spatial distributions,provides essential evidence for developing effective prevention and control strategies.Methods:Data for 14 types of VBDs from 2005 to 2024 were obtained from the China National Infectious Disease Surveillance System.These diseases were categorized as mosquito-borne,tick-borne,rodent-borne,and other VBDs.Using the Mann-Kendall trend test,we analyzed demographic characteristics,spatial distribution,temporal trends,and seasonal patterns of notified cases over the 20-year period.Results:From 2005 to 2024,a total of 1,129,736 VBD cases were reported in China.Scrub typhus(28.17%),malaria(20.8%),hemorrhagic fever with renal syndrome(HFRS,18.4%),dengue(12.61%),and schistosomiasis(8.42%)collectively accounted for 88.4%of all cases.Over a 20-year period,mosquitoborne and rodent-borne diseases indicated significant declining trends(P<0.05),while tick-borne and other VBDs demonstrated significant increasing trends(P<0.05).Dengue,scrub typhus,and severe fever with thrombocytopenia syndrome(SFTS)expanded geographically,with annual increases of 10.89,12.37,and 7.07 reporting cities,respectively.Although diseases such as plague,malaria,and schistosomiasis have been effectively controlled,the incidence of scrub typhus,dengue,HFRS,and SFTS has remained high in recent years.Conclusions:The burden of VBDs in China remains substantial,with an increasing trend observed over the past 5 years.The rising incidence and geographic expansion of scrub typhus,dengue,and SFTS warrant particular attention from public health authorities.
基金This research portfolio received funding support from the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases(TDR)Geneva,Switzerland and the International Development Research Center,Canada.
文摘Background:Diseases transmitted to humans by vectors account for 17%of all infectious diseases and remain significant public health problems.Through the years,great strides have been taken towards combatting vectorborne diseases(VBDs),most notably through large scale and coordinated control programmes,which have contributed to the decline of the global mortality attributed to VBDs.However,with environmental changes,including climate change,the impact on VBDs is anticipated to be significant,in terms of VBD-related hazards,vulnerabilities and exposure.While there is growing awareness on the vulnerability of the African continent to VBDs in the context of climate change,there is still a paucity of research being undertaken in this area,and impeding the formulation of evidence-based health policy change.Main body:One way in which the gap in knowledge and evidence can be filled is for donor institutions to support research in this area.The collaboration between the WHO Special Programme for Research and Training in Tropical Diseases(TDR)and the International Centre for Research and Development(IDRC)builds on more than 10 years of partnership in research capacity-building in the field of tropical diseases.From this partnership was born yet another research initiative on VBDs and the impact of climate change in the Sahel and sub-Saharan Africa.This paper lists the projects supported under this research initiative and provides a brief on some of the policy and good practice recommendations emerging from the ongoing implementation of the research projects.Conclusion:Data generated from the research initiative are expected to be uptaken by stakeholders(including communities,policy makers,public health practitioners and other relevant partners)to contribute to a better understanding of the impacts of social,environmental and climate change on VBDs(i.e.the nature of the hazard,vulnerabilities,exposure),and improve the ability of African countries to adapt to and reduce the effects of these changes in ways that benefit their most vulnerable populations.
基金Valery Ridde holds a CIHR-funded Research Chair in Applied Public Health(CPP-137901).
文摘This paper highlights the critical importance of evidence on vector-borne diseases(VBD)prevention and control interventions in urban settings when assessing current and future needs,with a view to setting policy priorities that promote inclusive and equitable urban health services.Research should produce knowledge about policies and interventions that are intended to control and prevent VBDs at the population level and to reduce inequities.Such interventions include policy,program,and resource distribution approaches that address the social determinants of health and exert influence at organizational and system levels.
基金Funding for the work came from WHO PO 21353027(PI MCT)in support of WHO-TDR IDRC-funded project:“Population health vulnerabilities to vectorborne diseases:increasing resilience under climate change conditions in Africa”WHO PO 201487225(PI MCT)as a technical contribution to the Global Framework for Climate Services.ÁM was supported via the Atmospheric and Oceanic Sciences(AOS)Program at Princeton University.
文摘Background:Climate-based disease forecasting has been proposed as a potential tool in climate change adaptation for the health sector.Here we explore the relevance of climate data,drivers and predictions for vector-borne disease control efforts in Africa.Methods:Using data from a number of sources we explore rainfall and temperature across the African continent,from seasonality to variability at annual,multi-decadal and timescales consistent with climate change.We give particular attention to three regions defined as WHO-TDR study zones in Western,Eastern and Southern Africa.Our analyses include 1)time scale decomposition to establish the relative importance of year-to-year,decadal and long term trends in rainfall and temperature;2)the impact of the El Niño Southern Oscillation(ENSO)on rainfall and temperature at the Pan African scale;3)the impact of ENSO on the climate of Tanzania using high resolution climate products and 4)the potential predictability of the climate in different regions and seasons using Generalized Relative Operating Characteristics.We use these analyses to review the relevance of climate forecasts for applications in vector borne disease control across the continent.Results:Timescale decomposition revealed long term warming in all three regions of Africa-at the level of 0.1-0.3°C per decade.Decadal variations in rainfall were apparent in all regions and particularly pronounced in the Sahel and during the East African long rains(March-May).Year-to-year variability in both rainfall and temperature,in part associated with ENSO,were the dominant signal for climate variations on any timescale.Observed climate data and seasonal climate forecasts were identified as the most relevant sources of climate information for use in early warning systems for vector-borne diseases but the latter varied in skill by region and season.Conclusions:Adaptation to the vector-borne disease risks of climate variability and change is a priority for government and civil society in African countries.Understanding rainfall and temperature variations and trends at multiple timescales and their potential predictability is a necessary first step in the incorporation of relevant climate information into vector-borne disease control decision-making.
文摘Background:The control of vector-borne diseases(VBD)is one of the greatest challenges on the global health agenda.Rapid and uncontrolled urbanization has heightened the interest in addressing these challenges through an integrated vector management(IVM)approach.The aim was to identify components related to impacts,economic evaluation,and sustainability that might contribute to this integrated approach to VBD prevention.Main body:We conducted a scoping review of available literature(2000-2016)using PubMed,Web of Science,Cochrane,CINAHL,Econlit,LILACS,Global Health Database,Scopus,and Embase,as well as Tropical Diseases Bulletin,WHOLIS,WHO Pesticide Evaluation Scheme,and Google Scholar.MeSH terms and free-text terms were used.A data extraction form was used,including TIDieR and ASTAIRE.MMAT and CHEERS were used to evaluate quality.Of the 42 documents reviewed,30 were focused on dengue,eight on malaria,and two on leishmaniasis.More than a half of the studies were conducted in the Americas.Half used a quantitative descriptive approach(n=21),followed by cluster randomized controlled trials(n=11).Regarding impacts,outcomes were:a)use of measures for vector control;b)vector control;c)health measures;and d)social measures.IVM reduced breeding sites,the entomology index,and parasite rates.Results were heterogeneous,with variable magnitudes,but in all cases were favourable to the intervention.Evidence of IVM impacts on health outcomes was very limited but showed reduced incidence.Social outcomes were improved abilities and capacities,empowerment,and community knowledge.Regarding economic evaluation,only four studies performed an economic analysis,and intervention benefits outweighed costs.Costeffectiveness was dependent on illness incidence.The results provided key elements to analyze sustainability in terms of three dimensions(social,economic,and environmental),emphasizing the implementation of a community-focused eco-bio-social approach.Conclusions:IVM has an impact on reducing vector breeding sites and the entomology index,but evidence of impacts on health outcomes is limited.Social outcomes are improved abilities and capacities,empowerment,and community knowledge.Economic evaluations are scarce,and cost-effectiveness is dependent on illness incidence.Community capacity building is the main component of sustainability,together with collaboration,institutionalization,and routinization of activities.Findings indicate a great heterogeneity in the interventions and highlight the need for characterizing interventions rigorously to facilitate transferability.
基金partly supported by the Yan’an University Qin Chuanyuan“Scientist+Engineer”Team Special Fund,No.2023KXJ-012(to YL)Yan’an University Transformation of Scientific and Technological Achievements Fund,No.2023CGZH-001(to YL)+2 种基金College Students Innovation and Entrepreneurship Training Program,Nos.D2023158,202410719056(to XS,JM)Yan’an University Production and Cultivation Project,No.CXY202001(to YL)Kweichow Moutai Hospital Research and Talent Development Fund Project,No.MTyk2022-25(to XO)。
文摘The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.
基金the financial assistance of the European Union(Grant no.ARISE-PP-FA-072),through the African Research Initiative for Scientific Excellence(ARISE),pilot programme.ARISE is implemented by the African Academy of Sciences with support from the European Commission and the African Union Commission.
文摘We look at the link between climate change and vector-borne diseases in low-and middle-income countries in Africa.The large endemicity and escalating threat of diseases such as malaria and arboviral diseases,intensified by climate change,disproportionately affects vulnerable communities globally.We highlight the urgency of prioritizing research and development,advocating for robust scientific inquiry to promote adaptation strategies,and the vital role that the next generation of African research leaders will play in addressing these challenges.Despite significant challenges such as funding shortages within countries,various pan-African-oriented funding bodies such as the African Academy of Sciences,the Africa Research Excellence Fund,the Wellcome Trust,the U.S.National Institutes of Health,and the Bill and Melinda Gates Foundation as well as initiatives such as the African Research Initiative for Scientific Excellence and the Pan-African Mosquito Control Association,have empowered(or are empowering)these researchers by supporting capacity building activities,including continental and global networking,skill development,mentoring,and African-led research.This article underscores the urgency of increased national investment in research,proposing the establishment of research government agencies to drive evidence-based interventions.Collaboration between governments and scientific communities,sustained by pan-African funding bodies,is crucial.Through these efforts,African nations are likely to enhance the resilience and adaptive capacity of their systems and communities by navigating these challenges effectively,fostering scientific excellence and implementing transformative solutions against climate-sensitive vector-borne diseases.
文摘Background:In 2015,following a call for proposals from the Special Programme for Research and Training in Tropical Diseases(TDR),six scoping reviews on the prevention and control of vector-borne diseases in urban areas were conducted.Those reviews provided a clear picture of the available knowledge and highlighted knowledge gaps,as well as needs and opportunities for future research.Based on the research findings of the scoping reviews,a concept mapping exercise was undertaken to produce a list of priority research needs to be addressed.Methods:Members of the six research teams responsible for the“VEctor boRne DiseAses Scoping reviews”(VERDAS)consortium’s scoping reviews met for 2 days with decision-makers from Colombia,Brazil,Peru,Pan-American Health Organization,and World Health Organization.A total of 11 researchers and seven decision-makers(from ministries of health,city and regional vector control departments,and vector control programs)completed the concept mapping,answering the question:“In view of the knowledge synthesis and your own expertise,what do we still need to know about vector-borne diseases and other infectious diseases of poverty in urban areas?”Participants rated each statement on two scales from 1 to 5,one relative to‘priority’and the other to‘policy relevance’,and grouped statements into clusters based on their own individual criteria and expertise.Results:The final map consisted of 12 clusters.Participants considered those entitled“Equity”,“Technology”,and“Surveillance”to have the highest priority.The cluster considered the most important concerns equity issues,confirming that these issues are rarely addressed in research on vector-borne diseases.On the other hand,the“Population mobility”and“Collaboration”clusters were considered to be the lowest priority but remained identified by participants as research priorities.The average policy relevance scores for each of the 12 clusters were roughly the same as the priority scores for all clusters.Some issues were not addressed during the brain-storming.This is the case for governance and for access and quality of care.Conclusions:Based on this work,and adopting a participatory approach,the concept mapping exercise conducted collaboratively with researchers from these teams and high-level decision-makers identified research themes for which studies should be carried out as a priority.
基金supported by grants from Tianjin Scientific Research Project in Key Areas of Traditional Chinese Medicine,Tianjin Municipal Health Commission,No.2024012(to JL)Tianjin Municipal Education Commission Project,No.2021KJ217(to CS)。
文摘Peroxisome proliferator-activated receptor alpha is a member of the nuclear hormone receptor superfamily and functions as a transcription factor involved in regulating cellular metabolism.Previous studies have shown that PPARαplays a key role in the onset and progression of neurodegenerative diseases.Consequently,peroxisome proliferator-activated receptor alpha agonists have garnered increasing attention as potential treatments for neurological disorders.This review aims to clarify the research progress regarding peroxisome proliferator-activated receptor alpha in nervous system diseases.Peroxisome proliferator-activated receptor alpha is present in all cell types within adult mouse and adult neural tissues.Although it is conventionally believed to be primarily localized in the nucleus,its function may be regulated by a dynamic balance between cytoplasmic and nuclear shuttling.Both endogenous and exogenous peroxisome proliferator-activated receptor alpha agonists bind to the peroxisome proliferator-activated response element to exert their biological effects.Peroxisome proliferator-activated receptor alpha plays a significant therapeutic role in neurodegenerative diseases.For instance,peroxisome proliferator-activated receptor alpha agonist gemfibrozil has been shown to reduce levels of soluble and insoluble amyloid-beta in the hippocampus of Alzheimer's disease mouse models through the autophagy-lysosomal pathway.Additionally,peroxisome proliferator-activated receptor alpha is essential for the normal development and functional maintenance of the substantia nigra,and it can mitigate motor dysfunction in Parkinson's disease mouse models.Furthermore,peroxisome proliferator-activated receptor alpha has been found to reduce neuroinflammation and oxidative stress in various neurological diseases.In summary,peroxisome proliferator-activated receptor alpha plays a crucial role in the onset and progression of multiple nervous system diseases,and peroxisome proliferator-activated receptor alpha agonists hold promise as new therapeutic agents for the treatment of neurodegenerative diseases,providing new options for patient care.
基金supported by The University of Hong Kong,China(109000487,109001694,204610401,and 204610519)National Natural Science Foundation of China(82402225)(to JH).
文摘Chemical exchange saturation transfer magnetic resonance imaging is an advanced imaging technique that enables the detection of compounds at low concentrations with high sensitivity and spatial resolution and has been extensively studied for diagnosing malignancy and stroke.In recent years,the emerging exploration of chemical exchange saturation transfer magnetic resonance imaging for detecting pathological changes in neurodegenerative diseases has opened up new possibilities for early detection and repetitive scans without ionizing radiation.This review serves as an overview of chemical exchange saturation transfer magnetic resonance imaging with detailed information on contrast mechanisms and processing methods and summarizes recent developments in both clinical and preclinical studies of chemical exchange saturation transfer magnetic resonance imaging for Alzheimer’s disease,Parkinson’s disease,multiple sclerosis,and Huntington’s disease.A comprehensive literature search was conducted using databases such as PubMed and Google Scholar,focusing on peer-reviewed articles from the past 15 years relevant to clinical and preclinical applications.The findings suggest that chemical exchange saturation transfer magnetic resonance imaging has the potential to detect molecular changes and altered metabolism,which may aid in early diagnosis and assessment of the severity of neurodegenerative diseases.Although promising results have been observed in selected clinical and preclinical trials,further validations are needed to evaluate their clinical value.When combined with other imaging modalities and advanced analytical methods,chemical exchange saturation transfer magnetic resonance imaging shows potential as an in vivo biomarker,enhancing the understanding of neuropathological mechanisms in neurodegenerative diseases.
基金supported by the National Key Research and Development Program of China,No.2022YFC2703101(to YC)the National Natural Science Fundation of China,No.82371422(to YC)+1 种基金the National Innovation and Entrepreneurship Training Program for College Students,No.202310611408(to XW)the 1·3·5 Project for Disciplines of Excellence Clinical Research Fund,West China Hospital,Sichuan University,No.2023HXFH032(to YC)。
文摘Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions.They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute course contingent upon the site of damage.The main types include amyotrophic lateral sclerosis,progressive muscular atrophy,primary lateral sclerosis,and progressive bulbar palsy,the pathological processes of which are largely identical,with the main disparity lying in the location of the lesions.Amyotrophic lateral sclerosis is the representative condition in this group of diseases,while other types are its variants.Hence,this article mainly focuses on the advancements and challenges in drug research for amyotrophic lateral sclerosis but also briefly addresses several other important degenerative motor neuron diseases.Although the precise pathogenesis remains elusive,recent advancements have shed light on various theories,including gene mutation,excitatory amino acid toxicity,autoimmunology,and neurotrophic factors.The US Food and Drug Administration has approved four drugs for use in delaying the progression of amyotrophic lateral sclerosis:riluzole,edaravone,AMX0035,and tofersen,with the latter being the most recent to receive approval.However,following several phaseⅢtrials that failed to yield favorable outcomes,AMX0035 has been voluntarily withdrawn from both the US and Canadian markets.This article presents a comprehensive summary of drug trials primarily completed between January 1,2023,and June 30,2024,based on data sourced from clinicaltrials.gov.Among these trials,five are currently in phaseⅠ,seventeen are in phaseⅡ,and eleven are undergoing phaseⅢevaluation.Notably,24 clinical trials are now investigating potential disease-modifying therapy drugs,accounting for the majority of the drugs included in this review.Some promising drugs being investigated in preclinical studies,such as ATH-1105,are included in our analysis,and another review in frontiers in gene therapy and immunotherapy has demonstrated their therapeutic potential for motor neuron diseases.This article was written to be an overview of research trends and treatment prospects related to motor neuron disease drugs,with the aim of highlighting the latest potentialities for clinical therapy.
基金supported by the National Natural Science Foundation of China,No.22103055(to JG)the Natural Science Foundation of Hebei Province,No.F2024110001(to HC)Open Project of Tianjin Key Laboratory of Optoelectronic Detection Technology and System,Nos.2024LODTS215(to NL),2024LODTS216(to XS).
文摘In recent years,exosomes have garnered extensive attention as therapeutic agents and early diagnostic markers in neurodegenerative disease research.Exosomes are small and can effectively cross the blood-brain barrier,allowing them to target deep brain lesions.Recent studies have demonstrated that exosomes derived from different cell types may exert therapeutic effects by regulating the expression of various inflammatory cytokines,mRNAs,and disease-related proteins,thereby halting the progression of neurodegenerative diseases and exhibiting beneficial effects.However,exosomes are composed of lipid bilayer membranes and lack the ability to recognize specific target cells.This limitation can lead to side effects and toxicity when they interact with non-specific cells.Growing evidence suggests that surface-modified exosomes have enhanced targeting capabilities and can be used as targeted drug-delivery vehicles that show promising results in the treatment of neurodegenerative diseases.In this review,we provide an up-to-date overview of existing research aimed at devising approaches to modify exosomes and elucidating their therapeutic potential in neurodegenerative diseases.Our findings indicate that exosomes can efficiently cross the blood-brain barrier to facilitate drug delivery and can also serve as early diagnostic markers for neurodegenerative diseases.We introduce the strategies being used to enhance exosome targeting,including genetic engineering,chemical modifications(both covalent,such as click chemistry and metabolic engineering,and non-covalent,such as polyvalent electrostatic and hydrophobic interactions,ligand-receptor binding,aptamer-based modifications,and the incorporation of CP05-anchored peptides),and nanomaterial modifications.Research into these strategies has confirmed that exosomes have significant therapeutic potential for neurodegenerative diseases.However,several challenges remain in the clinical application of exosomes.Improvements are needed in preparation,characterization,and optimization methods,as well as in reducing the adverse reactions associated with their use.Additionally,the range of applications and the safety of exosomes require further research and evaluation.
基金supported by grants from Guangdong Basic and Applied Basic Research Foundation,No.2021A1515110801(to SW)the National Natural Science Foundation of China,No.82301511(to SW)+1 种基金“Double First-Class”Construction Project of NPU,Nos.0515023GH0202320(to JC),0515023SH0201320(to JC)973 Program,No.2011CB504100(to JC).
文摘Myelination,the continuous ensheathment of neuronal axons,is a lifelong process in the nervous system that is essential for the precise,temporospatial conduction of action potentials between neurons.Myelin also provides intercellular metabolic support to axons.Even minor disruptions in the integrity of myelin can impair neural performance and increase susceptibility to neurological diseases.In fact,myelin degeneration is a well-known neuropathological condition that is associated with normal aging and several neurodegenerative diseases,including multiple sclerosis and Alzheimer’s disease.In the central nervous system,compact myelin sheaths are formed by fully mature oligodendrocytes.However,the entire oligodendrocyte lineage is susceptible to changes in the biological microenvironment and other risk factors that arise as the brain ages.In addition to their well-known role in action potential propagation,oligodendrocytes also provide intercellular metabolic support to axons by transferring energy metabolites and delivering exosomes.Therefore,myelin degeneration in the aging central nervous system is a significant contributor to the development of neurodegenerative diseases.Interventions that mitigate age-related myelin degeneration can improve neurological function in aging individuals.In this review,we investigate the changes in myelin that are associated with aging and their underlying mechanisms.We also discuss recent advances in understanding how myelin degeneration in the aging brain contributes to neurodegenerative diseases and explore the factors that can prevent,slow down,or even reverse age-related myelin degeneration.Future research will enhance our understanding of how reducing age-related myelin degeneration can be used as a therapeutic target for delaying or preventing neurodegenerative diseases.
基金supported by the National Natural Science Foundation of China,No.82160255(to RX)the Natural Science Foundation of Jiangxi Province,No.20212BAB216026(to HL)+2 种基金Science and Technology Plan Project of Health Commission of Jiangxi Province,No.202110016(to HL)Science and Technology Plan Project of Jiangxi Provincial Administration of Traditional Chinese Medicine,No.2022B975(to HL)a grant from Jiangxi Province Key Laboratory of Neurology,No.2024SSY06081(to RX).
文摘With the gradual advancement of research methods and technologies,various biological processes have been identified as playing roles in the pathogenesis of neurodegenerative diseases.However,current descriptions of these biological processes do not fully explain the onset,progression,and development of these conditions.Therefore,exploration of the pathogenesis of neurodegenerative diseases remains a valuable area of research.This review summarizes the potential common pathogeneses of Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,Huntington’s disease,frontotemporal lobar dementia,and Lewy body disease.Research findings have indicated that several common biological processes,including aging,genetic factors,progressive neuronal dysfunction,neuronal death and apoptosis,protein misfolding and aggregation,neuroinflammation,mitochondrial dysfunction,axonal transport defects,and gut microbiota dysbiosis,are involved in the pathogenesis of these six neurodegenerative diseases.Based on current information derived from diverse areas of research,these biological processes may form complex pathogenic networks that lead to distinctive types of neuronal death in neurodegenerative diseases.Furthermore,promoting the regeneration of damaged neurons may be achievable through the repair of affected neural cells if the underlying pathogenesis can be prevented or reversed.Hence,these potential common biological processes may represent only very small,limited elements within numerous intricate pathogenic networks associated with neurodegenerative diseases.In clinical treatment,interfering with any single biological process has proven insufficient to completely halt the progression of neurodegenerative diseases.Therefore,future research on the pathogenesis of neurodegenerative diseases should focus on uncovering the complex pathogenic networks,rather than isolating individual biological processes.Based on this,therapies that aim to block or reverse various targets involved in the potential pathogenic mechanisms of neurodegenerative diseases may be promising directions,as current treatment methods that focus on halting a single pathogenic factor have not achieved satisfactory efficacy.
基金funded by the Science and Technology Research of Henan Province,No.242103810041(to JY)。
文摘For diverse neurodegenerative disorders,microglial cells are activated.Furthermore,dysfunctional and hyperactivated microglia initiate mitochondrial autophagy,oxidative stress,and pathological protein accumulation,ending with neuroinflammation that exacerbates damage to dopaminergic neurons and contributes significantly to the pathology of neurodegenerative disorder.Microglial overactivation is closely associated with the secretion of pro-inflammatory cytokines,the phagocytosis of injured neurons,and the modulation of neurotoxic environments.This review summarizes the role of microglia neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease,multiple sclerosis,multiple system atrophy,amyotrophic lateral sclerosis,frontotemporal dementia,progressive supranuclear palsy,cortical degeneration,Lewy body dementia,and Huntington's disease.It also discusses novel forms of cell death such as ferroptosis,cuproptosis,disulfidptosis,and parthanatos(poly(adenosine diphosphate ribose)polymerase 1-dependent cell death),as well as the impact of regulatory factors related to microglial inflammation on microglial activation and neuroinflammation.The aim is to identify potential targets for microglial cell therapy in neurodegenerative diseases.
基金supported by Yunnan Provincial Science and Technology Department,Nos.202403AC100007(to NZ),202301AY070001-239(to JY)Yunnan Revitalization Talent Support Program,Nos.2019-069(to ZY)and 2019-300(to JY)+1 种基金the National Natural Science Foundation of China,Nos.32260196(to JY)a grant from Kunming Medical University,No.2024S085(to KL)。
文摘Neurodegenerative diseases are a group of illnesses characterized by the gradual deterioration of the central nervous system,leading to a decline in patients'cognitive,motor,and emotional abilities.Neuroinflammation plays a significant role in the progression of these diseases.However,there is limited research on therapeutic approaches to specifically target neuroinflammation.The role of T lymphocytes,which are crucial mediators of the adaptive immune response,in neurodegenerative diseases has been increasingly recognized.This review focuses on the involvement of T lymphocytes in the neuroinflammation associated with neurodegenerative diseases.The pathogenesis of neurodegenerative diseases is complex,involving multiple mechanisms and pathways that contribute to the gradual degeneration of neurons,and T cells are a key component of these processes.One of the primary factors driving neuroinflammation in neurodegenerative diseases is the infiltration of T cells and other neuroimmune cells,including microglia,astrocytes,B cells,and natural killer cells.Different subsets of CD4~+T cells,such as Th1,Th2,Th17,and regulatory T cells,can differentiate into various cell types and perform distinct roles within the neuroinflammatory environment of neurodegenerative diseases.Additionally,CD8~+T cells,which can directly regulate immune responses and kill target cells,also play several important roles in neurodegenerative diseases.Clinical trials investigating targeted T cell therapies for neurodegenerative diseases have shown that,while some patients respond positively,others may not respond as well and may even experience adverse effects.Targeting T cells precisely is challenging due to the complexity of immune responses in the central nervous system,which can lead to undesirable side effects.However,with new insights into the pathophysiology of neurodegenerative diseases,there is hope for the establishment of a solid theoretical foundation upon which innovative treatment strategies that target T cells can be developed in the future.
基金supported by the Grant PID2021-126715OB-IOO financed by MCIN/AEI/10.13039/501100011033 and"ERDFA way of making Europe"by the Grant PI22CⅢ/00055 funded by Instituto de Salud CarlosⅢ(ISCⅢ)+6 种基金the UFIECPY 398/19(PEJ2018-004965) grant to RGS funded by AEI(Spain)the UFIECPY-396/19(PEJ2018-004961)grant financed by MCIN (Spain)FI23CⅢ/00003 grant funded by ISCⅢ-PFIS Spain) to PMMthe UFIECPY 328/22 (PEJ-2021-TL/BMD-21001) grant to LM financed by CAM (Spain)the grant by CAPES (Coordination for the Improvement of Higher Education Personnel)through the PDSE program (Programa de Doutorado Sanduiche no Exterior)to VSCG financed by MEC (Brazil)
文摘The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.
