Alcohol use disorder(AUD)is a medical condition that impairs a person's ability to stop or manage their drinking in the face of negative social,occupational,or health consequences.AUD is defined by the National In...Alcohol use disorder(AUD)is a medical condition that impairs a person's ability to stop or manage their drinking in the face of negative social,occupational,or health consequences.AUD is defined by the National Institute on Alcohol Abuse and Alcoholism as a"severe problem".The central nervous system is the primary target of alcohol's adverse effects.It is crucial to identify various neurological disorders associated with AUD,including alcohol withdrawal syndrome,Wernicke-Korsakoff syndrome,Marchiafava-Bignami disease,dementia,and neuropathy.To gain a better understanding of the neurological environment of alcoholism and to shed light on the role of various neurotransmitters in the phenomenon of alcoholism.A comprehensive search of online databases,including PubMed,EMBASE,Web of Science,and Google Scholar,was conducted to identify relevant articles.Several neurotransmitters(dopamine,gammaaminobutyric acid,serotonin,and glutamate)have been linked to alcoholism due to a brain imbalance.Alcoholism appears to be a complex genetic disorder,with variations in many genes influencing risk.Some of these genes have been identified,including two alcohol metabolism genes,alcohol dehydrogenase 1B gene and aldehyde dehydrogenase 2 gene,which have the most potent known effects on the risk of alcoholism.Neuronal degeneration and demyelination in people with AUD may be caused by neuronal damage,nutrient deficiencies,and blood brain barrier dysfunction;however,the underlying mechanism is unknown.This review will provide a detailed overview of the neurobiology of alcohol addiction,followed by recent studies published in the genetics of alcohol addiction,molecular mechanism and detailed information on the various acute and chronic neurological manifestations of alcoholism for the Future research.展开更多
Ferroptosis is a form of cell death elicited by an imbalance in intracellular iron concentrations,leading to enhanced lipid peroxidation.In neurological disorders,both oxidative stress and mitochondrial damage can con...Ferroptosis is a form of cell death elicited by an imbalance in intracellular iron concentrations,leading to enhanced lipid peroxidation.In neurological disorders,both oxidative stress and mitochondrial damage can contribute to ferroptosis,resulting in nerve cell dysfunction and death.The ubiquitin-proteasome system(UPS)refers to a cellular pathway in which specific proteins are tagged with ubiquitin for recognition and degradation by the proteasome.In neuro-logical conditions,the UPS plays a significant role in regu-lating ferroptosis.In this review,we outline how the UPS regulates iron metabolism,ferroptosis,and their interplay in neurological diseases.In addition,we discuss the future application of small-molecule inhibitors and identify poten-tial drug targets.Further investigation into the mechanisms of UPS-mediated ferroptosis will provide novel insights and strategies for therapeutic interventions and clinical applica-tions in neurological diseases.展开更多
The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central n...The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central nervous system, with sensory stimulation and excitation conduction functions. Astrocytes and microglia belong to the glial cell family, which is the main source of cytokines and represents the main defense system of the central nervous system. Nerve cells undergo neurotransmission or gliotransmission, which regulates neuronal activity via the ion channels, receptors, or transporters expressed on nerve cell membranes. Ion channels, composed of large transmembrane proteins, play crucial roles in maintaining nerve cell homeostasis. These channels are also important for control of the membrane potential and in the secretion of neurotransmitters. A variety of cellular functions and life activities, including functional regulation of the central nervous system, the generation and conduction of nerve excitation, the occurrence of receptor potential, heart pulsation, smooth muscle peristalsis, skeletal muscle contraction, and hormone secretion, are closely related to ion channels associated with passive transmembrane transport. Two types of ion channels in the central nervous system, potassium channels and calcium channels, are closely related to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Accordingly, various drugs that can affect these ion channels have been explored deeply to provide new directions for the treatment of these neurological disorders. In this review, we focus on the functions of potassium and calcium ion channels in different nerve cells and their involvement in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, epilepsy, autism, and rare disorders. We also describe several clinical drugs that target potassium or calcium channels in nerve cells and could be used to treat these disorders. We concluded that there are few clinical drugs that can improve the pathology these diseases by acting on potassium or calcium ions. Although a few novel ion-channelspecific modulators have been discovered, meaningful therapies have largely not yet been realized. The lack of target-specific drugs, their requirement to cross the blood–brain barrier, and their exact underlying mechanisms all need further attention. This review aims to explain the urgent problems that need research progress and provide comprehensive information aiming to arouse the research community's interest in the development of ion channel-targeting drugs and the identification of new therapeutic targets for that can increase the cure rate of nervous system diseases and reduce the occurrence of adverse reactions in other systems.展开更多
BACKGROUND Artificial intelligence(AI)has become significantly integrated into healthcare,particularly in the diag-nosing of neurological disorders.This advancement has enabled neurologists and physicians to diagnose ...BACKGROUND Artificial intelligence(AI)has become significantly integrated into healthcare,particularly in the diag-nosing of neurological disorders.This advancement has enabled neurologists and physicians to diagnose conditions more quickly and effectively,ultimately benefiting patients.AIM To explore the current status and key highlights of AI-related articles in diagnosing of neurological disorders.METHODS A systematic literature review was conducted in the Web of Science Core Collection database using the following strategy:TS=("Artificial Intelligence"OR"Computational Intelligence"OR"Machine Learning"OR"AI")AND TS=("Neurological disorders"OR"CNS disorder"AND"diagnosis").The search was limited to articles and reviews.Microsoft Excel 2019 and VOSviewer were utilized to identify major contributors,including authors,institutions,countries,and journals.Additionally,VOSviewer was employed to analyze and visualize current trends and hot topics through network visualization maps.RESULTS A total of 276 publications from 2000 to 2024 were retrieved.The United States,India,and China emerged as the top contributors in this field.Major institutions included Johns Hopkins University,King's College London,and Harvard Medical School.The most prolific author was U.Rajendra Acharya from the University of Southern Queensland(Australia).Among journals,IEEE Access,Scientific Reports,and Sensors were the most productive,while Frontiers in Neuroscience led in total citations.Central topics in AI-related articles on neurological disorders diagnosis included Alzheimer's disease,Parkinson's disease,dementia,epilepsy,autism,attention deficit hyperactivity disorder,and their intersections with deep learning and AI.CONCLUSION Research on AI's role in diagnosing neurological disorders is becoming widely recognized for its growing importance.AI shows promise in diagnosing various neurological disorders,yet requires further improvement and extensive future research.展开更多
Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein functio...Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted therapies.To investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary time.Genetic tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological diseases.Drosophila boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug candidates.Researchers can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical trials.In this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic implications.We discuss rare diseases associated with both neuron-expressed and glial-expressed genes.Specific cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal movements.And we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell syndrome.Loss-of-function mutations in ACOX1 result in ACOX1 deficiency,characterized by very-long-chain fatty acid accumulation and glial degeneration.Notably,this review highlights how modeling these diseases in Drosophila has provided valuable insights into their pathophysiology,offering a platform for the rapid identification of potential therapeutic interventions.Rare neurological diseases involve a wide range of expression systems,and sometimes common phenotypes can be found among different genes that cause abnormalities in neurons or glia.Furthermore,mutations within the same gene may result in varying functional outcomes,such as complete loss of function,partial loss of function,or gain-of-function mutations.The phenotypes observed in patients can differ significantly,underscoring the complexity of these conditions.In conclusion,Drosophila represents an indispensable and cost-effective tool for investigating rare neurological diseases.By facilitating the modeling of these conditions,Drosophila contributes to a deeper understanding of their genetic basis,pathophysiology,and potential therapies.This approach accelerates the discovery of promising drug candidates,ultimately benefiting patients affected by these complex and understudied diseases.展开更多
Perivascular space(PVS) is a crevice between two slices of cerebral pia maters,filled with tissue fluid,which be formed by pia mater emboling in the surrounding of cerebral perforating branch(excluding micrangium). No...Perivascular space(PVS) is a crevice between two slices of cerebral pia maters,filled with tissue fluid,which be formed by pia mater emboling in the surrounding of cerebral perforating branch(excluding micrangium). Normal PVS(diameter < 2 mm) can be found in almost all healthy adults; however enlarged PVS(diameter > 2 mm) has correlation with neurological disorders probably. The article reviews the formation mechanism,imageology characteristics and the relation with neurological disorders of PVS,which...展开更多
Extraintestinal manifestations occur in about one-third of patients living with inflammatory bowel disease(IBD) and may precede the onset of gastrointestinal symptoms by many years. Neurologic disorders associated wit...Extraintestinal manifestations occur in about one-third of patients living with inflammatory bowel disease(IBD) and may precede the onset of gastrointestinal symptoms by many years. Neurologic disorders associated with IBD are not frequent, being reported in 3% of patients, but they often represent an important cause of morbidity and a relevant diagnostic issue. In addition, the increasing use of immunosuppressant and biological therapies for IBD may also play a pivotal role in the development of neurological disorders of different type and pathogenesis. Hence, we provide a complete and profound review of the main features of neurological complications associated with IBD, with particular reference to those related to drugs and with a specific focus on their clinical presentation and possible pathophysiological mechanisms.展开更多
Mesenchymal stem cells are multipotent cells that possess anti-inflammatory,antiapoptotic and immunomodulatory properties.The effects of existing drugs for neurodegenerative disorders such as Alzheimer’s disease are ...Mesenchymal stem cells are multipotent cells that possess anti-inflammatory,antiapoptotic and immunomodulatory properties.The effects of existing drugs for neurodegenerative disorders such as Alzheimer’s disease are limited,thus mesenchymal stem cell therapy has been anticipated as a means of ameliorating neuronal dysfunction.Since mesenchymal stem cells are known to scarcely differentiate into neuronal cells in damaged brain after transplantation,paracrine factors secreted from mesenchymal stem cells have been suggested to exert therapeutic effects.Extracellular vesicles and exosomes are small vesicles released from mesenchymal stem cells that contain various molecules,including proteins,mRNAs and microRNAs.In recent years,administration of exosomes/extracellular vesicles in models of neurological disorders has been shown to improve neuronal dysfunctions,via exosomal transfer into damaged cells.In addition,various microRNAs derived from mesenchymal stem cells that regulate various genes and reduce neuropathological changes in various neurological disorders have been identified.This review summarizes the effects of exosomes/extracellular vesicles and exosomal microRNAs derived from mesenchymal stem cells on models of stroke,subarachnoid and intracerebral hemorrhage,traumatic brain injury,and cognitive impairments,including Alzheimer’s disease.展开更多
Synapsins serve as flagships among the presynaptic proteins due to their abundance on synaptic vesicles and contribution to synaptic communication. Several studies have emphasized the importance of this multi-gene fam...Synapsins serve as flagships among the presynaptic proteins due to their abundance on synaptic vesicles and contribution to synaptic communication. Several studies have emphasized the importance of this multi-gene family of neuron-specific phosphoproteins in maintaining brain physiology. In the recent times, increasing evidence has established the relevance of alterations in synapsins as a major determinant in many neurological disorders. Here,we give a comprehensive description of the diverse roles of the synapsin family and the underlying molecular mechanisms that contribute to several neurological disorders.These physiologically important roles of synapsins associated with neurological disorders are just beginning to be understood. A detailed understanding of the diversified expression of synapsins may serve to strategize novel therapeutic approaches for these debilitating neurological disorders.展开更多
It is well known that the gut microbiota plays an extremely important role in modulating host physiological functions such as immunity and metabolic homeostasis.In recent years,accumulated evidence has revealed that t...It is well known that the gut microbiota plays an extremely important role in modulating host physiological functions such as immunity and metabolic homeostasis.In recent years,accumulated evidence has revealed that the gut microbiota can regulate the functions of the central nervous system(CNS)through the gut-brain axis,which provides a novel insight into the interactions between the gut and brain.This review focuses on the molecular mechanism of the crosstalk between the gut microbiota and the brain via the gut-brain axis,and on the onset and development of neurological disorders triggered by gut microbiota dysbiosis.These topics are followed by a critical analysis of potential intervention strategies targeting gut microbiota dysbiosis,including the use of probiotics,prebiotics,synbiotics,and diets.While research on the microbiota-gut-brain axis is still in its relative infancy,clarifying the molecular mechanism that underlies how the gut microbiota regulates neurological functions not only holds the promise of revealing potentially novel pathogeneses of neurological disorders,but also may lead to the development of potential diagnosis biomarkers and intervention strategies targeting microbiota dysbiosis for neurological disorders.展开更多
Neurologic impairments are usually irreversible as a result of limited regeneration in the central nervous system.Therefore,based on the regenerative capacity of stem cells,transplantation therapies of various stem ce...Neurologic impairments are usually irreversible as a result of limited regeneration in the central nervous system.Therefore,based on the regenerative capacity of stem cells,transplantation therapies of various stem cells have been tested in basic research and preclinical trials,and some have shown great prospects.This manuscript overviews the cellular and molecular characteristics of embryonic stem cells,induced pluripotent stem cells,neural stem cells,retinal stem/progenitor cells,mesenchymal stem/stromal cells,and their derivatives in vivo and in vitro as sources for regenerative therapy.These cells have all been considered as candidates to treat several major neurological disorders and diseases,owing to their self-renewal capacity,multi-directional differentiation,neurotrophic properties,and immune modulation effects.We also review representative basic research and recent clinical trials using stem cells for neurodegenerative diseases,including Parkinson＇s disease,Alzheimer＇s disease,and age-related macular degeneration,as well as traumatic brain injury and glioblastoma.In spite of a few unsuccessful cases,risks of tumorigenicity,and ethical concerns,most results of animal experiments and clinical trials demonstrate efficacious therapeutic effects of stem cells in the treatment of nervous system disease.In summary,these emerging findings in regenerative medicine are likely to contribute to breakthroughs in the treatment of neurological disorders.Thus,stem cells are a promising candidate for the treatment of nervous system diseases.展开更多
The kallikrein-kinin system(KKS) is an intricate endogenous pathway involved in several physiological and pathological cascades in the brain. Due to the pathological effects of kinins in blood vessels and tissues, the...The kallikrein-kinin system(KKS) is an intricate endogenous pathway involved in several physiological and pathological cascades in the brain. Due to the pathological effects of kinins in blood vessels and tissues, their formation and degradation are tightly controlled. Their components have been related to several central nervous system diseases such as stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy and others. Bradykinin and its receptors(B1R and B2R) may have a role in the pathophysiology of certain central nervous system diseases. It has been suggested that kinin B1R is up-regulated in pathological conditions and has a neurodegenerative pattern, while kinin B2R is constitutive and can act as a neuroprotective factor in many neurological conditions. The renin angiotensin system(RAS) is an important blood pressure regulator and controls both sodium and water intake. AngⅡ is a potent vasoconstrictor molecule and angiotensin converting enzyme is the major enzyme responsible for its release. AngⅡ acts mainly on the AT1 receptor, with involvement in several systemic and neurological disorders. Brain RAS has been associated with physiological pathways, but is also associated with brain disorders. This review describes topics relating to the involvement of both systems in several forms of brain dysfunction and indicates components of the KKS and RAS that have been used as targets in several pharmacological approaches.展开更多
Deep transcranial magnetic stimulation(DTMS)is a new non-invasive neuromodulation technique based on repetitive transcranial magnetic stimulation technology.The new H-coil has significant advantages in the treatment a...Deep transcranial magnetic stimulation(DTMS)is a new non-invasive neuromodulation technique based on repetitive transcranial magnetic stimulation technology.The new H-coil has significant advantages in the treatment and mechanism research of psychiatric and neurological disorders.This is due to its deep stimulation site and wide range of action.This paper reviews the clinical progress of DTMS in psychiatric and neurological disorders such as Parkinson’s disease,Alzheimer’s disease,post-stroke motor dysfunction,aphasia,and other neurological disorders,as well as anxiety,depression,and schizophrenia.展开更多
Although therapeutic potential of neurotrophic factors(NTFs)has been well recognized for over two decades,attempts to translate that potential to the clinic have been disappointing,largely due to significant obstacle...Although therapeutic potential of neurotrophic factors(NTFs)has been well recognized for over two decades,attempts to translate that potential to the clinic have been disappointing,largely due to significant obstacles in delivery,including inadequate protein dose/kinetics released at target sites.Considerable efforts have been made to improve the therapeutic performance of NTFs.This articles reviews recent developments in localized delivery systems of NTFs for the neurological disorders treatments with a main focus on sustained delivery strategies.Different non-covalent binding approaches have been employed to immobilize proteins in hydrogels,microspheres,electrospun nanofibers,and their combined systems,which serve as depots for sustained local release of NTFs.The challenges associated with current NTFs delivery systems and how these systems can be applied to neurological diseases and disorders have been discussed in the review.In conclusion,optimal delivery systems for NTFs will be needed for reliable and meaningful clinical benefits;ideally,delivering a time and dose-controlled release of bioactive multiNTFs at different individual optimal kinetics to achieve multi-functions in target tissues is significant preferred.展开更多
Background and object:The burden of neurological disorders in India is expected to increase due to the rapid demographic and epidemiological transition,with irrational drug use,which is also a global concern.Thus,drug...Background and object:The burden of neurological disorders in India is expected to increase due to the rapid demographic and epidemiological transition,with irrational drug use,which is also a global concern.Thus,drug utilization evaluation is designed to ensure appropriate medicine use within the healthcare settings.The aim of the study was to assess the rate and pattern of drug utilization in the management of neurological disorders.Materials and methods:A hospital-based cross-sectional drug utilization evaluation study on neurological drugs was carried out at the Department of Neurology over a span of six months.All legible prescriptions consisting neurological medications irrespective of patient's gender,aged≥18 years were included for the study.The World Health Organization(WHO)core drug use indicators were used to assess the drug prescribing and utilization patterns.Results:A total of 310 prescriptions were reviewed,where male predominance was found to be 56.45%.Out of 310 prescriptions,drugs belonging to 26 neurological classes were prescribed for the management of various neurological disorders.The majority of patients were diagnosed with epilepsy and the most prescribed drugs per patient were phenytoin(14.8%)and valproic acid(6.45%).By following the WHO core drug prescribing indicators,65.47%of drugs prescribed from the India National List of Essential Medicines,2022,followed by 29.83%of drugs prescribed in generic name and 10.86%of prescriptions including injections.Conclusion:The study findings showed that the prescribing pattern in the Department of Neurology was in accordance with the WHO core prescribing indicators.But,the extent of polypharmacy prescriptions was very high.Therefore,interventions are very necessary to promote rational drug prescribing patterns and thus clinical pharmacists can contribute to assess and review the drug utilization pattern to optimize the drug therapy and improvement in patient safety.展开更多
Several diseases have been successfully modeled since the development of induced pluripotent stem cell(i PSC) technology in 2006. Since then, methods for increased reprogramming efficiency and cell culture maintenance...Several diseases have been successfully modeled since the development of induced pluripotent stem cell(i PSC) technology in 2006. Since then, methods for increased reprogramming efficiency and cell culture maintenance have been optimized and many protocols for differentiating stem cell lines have been successfully developed, allowing the generation of several cellular subtypes in vitro. Gene editing technologies have also greatly advanced lately, enhancing disease-specific phenotypes by creating isogenic cell lines, allowing mutations to be corrected in affected samples or inserted in control lines. Neurological disorders have benefited the most from i PSC-disease modeling for its capability for generating disease-relevant cell types in vitro from the central nervous system, such as neurons and glial cells, otherwise only available from post-mortem samples. Patient-specific i PSC-derived neural cells can recapitulate the phenotypes of these diseases and therefore, considerably enrich our understanding of pathogenesis, disease mechanism and facilitate the development of drug screening platforms for novel therapeutic targets. Here, we review the accomplishments and the current progress in human neurological disorders by using i PSC modeling for Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal muscular atrophy, amyotrophic lateral sclerosis, duchenne muscular dystrophy, schizophrenia and autism spectrum disorders, which include Timothy syndrome, Fragile X syndrome, Angelman syndrome, Prader-Willi syndrome, PhelanMc Dermid, Rett syndrome as well as Nonsyndromic Autism.展开更多
Random noise stimulation technique involves applying any form of energy(for instance,light,mechanical,electrical,sound)with unpredictable intensities through time to the brain or sensory receptors to enhance sensory,m...Random noise stimulation technique involves applying any form of energy(for instance,light,mechanical,electrical,sound)with unpredictable intensities through time to the brain or sensory receptors to enhance sensory,motor,or cognitive functions.Random noise stimulation initially employed mechanical noise in auditory and cutaneous stimuli,but electrical energies applied to the brain or the skin are becoming more frequent,with a series of clinical applications.Indeed,recent evidence shows that transcranial random noise stimulation can increase corticospinal excitability,improve cognitive/motor performance,and produce beneficial aftereffects at the behavioral and psychological levels.Here,we present a narrative review about the potential uses of random noise stimulation to treat neurological disorders,including attention deficit hyperactivity disorder,schizophrenia,amblyopia,myopia,tinnitus,multiple sclerosis,post-stroke,vestibular-postural disorders,and sensitivity loss.Many of the reviewed studies reveal that the optimal way to deliver random noise stimulation-based therapies is with the concomitant use of neurological and neuropsychological assessments to validate the beneficial aftereffects.In addition,we highlight the requirement of more randomized controlled trials and more physiological studies of random noise stimulation to discover another optimal way to perform the random noise stimulation interventions.展开更多
Neurological disorders are amongst the most widely studied human aliments.Yet,they are also one of the most poorly understood.Although most of these disorders are polygenic,genotype still plays an important role in th...Neurological disorders are amongst the most widely studied human aliments.Yet,they are also one of the most poorly understood.Although most of these disorders are polygenic,genotype still plays an important role in their etiologies.For example,in schizophrenia and autism spectrum disorders,there is a 40-60%concordance rate in monozygotic twins,with 60-90%heritability（Burmeister et al.,2008）.However,the mechanisms by which multiple genes and their genomic variations influence the phenotypes of the disorders remain to be understood. The complexities of the disorders are tur- ther compounded by the individual rarity of the genomic variations and their variable penetrance （Cook and Scherer, 2008）. Thus, conventional disease modeling, such as gene knockout in cells or in animals, to attain the desired disease genotype may not be the most suitable platform for tackling most neurological disorders.展开更多
This review reflects upon our own as well as other investigators’studies on the role of receptor for advanced glycation end-products(RAGE),bringing up the latest information on RAGE in physiology and pathology of the...This review reflects upon our own as well as other investigators’studies on the role of receptor for advanced glycation end-products(RAGE),bringing up the latest information on RAGE in physiology and pathology of the nervous system.Over the last ten years,major progress has been made in uncovering many of RAGE-ligand interactions and signaling pathways in nervous tissue;however,the translation of these discoveries into clinical practice has not come to fruition yet.This is likely,in part to be the result of our incomplete understanding of this crucial signaling pathway.Clinical trials examining the therapeutic efficacy of blocking RAGE-external ligand interactions by genetically engineered soluble RAGE or an endogenous RAGE antagonist,has not stood up to its promise;however,other trials with different blocking agents are being considered with hope for therapeutic success in diseases of the nervous system.展开更多
The central nervous system(CNS)is a reservoir of immune privilege.Specialized immune glial cells are responsible for maintenance and defense against foreign invaders.The blood–brain barrier(BBB)prevents detrimental p...The central nervous system(CNS)is a reservoir of immune privilege.Specialized immune glial cells are responsible for maintenance and defense against foreign invaders.The blood–brain barrier(BBB)prevents detrimental pathogens and potentially overreactive immune cells from entering the periphery.When the double-edged neuroinflammatory response is overloaded,it no longer has the protective function of promoting neuroregeneration.Notably,microbiota and its derivatives may emerge as pathogen-associated molecular patterns of brain pathology,causing microbiome–gut–brain axis dysregulation from the bottom-up.When dysbiosis of the gastrointestinal flora leads to subsequent alterations in BBB permeability,peripheral immune cells are recruited to the brain.This results in amplification of neuroinflammatory circuits in the brain,which eventually leads to specific neurological disorders.Aggressive treatment strategies for gastrointestinal disorders may protect against specific immune responses to gastrointestinal disorders,which can lead to potential protective effects in the CNS.Accordingly,this study investigated the mutual effects of microbiota and the gut–brain axis,which may provide targeting strategies for future disease treatment.展开更多
文摘Alcohol use disorder(AUD)is a medical condition that impairs a person's ability to stop or manage their drinking in the face of negative social,occupational,or health consequences.AUD is defined by the National Institute on Alcohol Abuse and Alcoholism as a"severe problem".The central nervous system is the primary target of alcohol's adverse effects.It is crucial to identify various neurological disorders associated with AUD,including alcohol withdrawal syndrome,Wernicke-Korsakoff syndrome,Marchiafava-Bignami disease,dementia,and neuropathy.To gain a better understanding of the neurological environment of alcoholism and to shed light on the role of various neurotransmitters in the phenomenon of alcoholism.A comprehensive search of online databases,including PubMed,EMBASE,Web of Science,and Google Scholar,was conducted to identify relevant articles.Several neurotransmitters(dopamine,gammaaminobutyric acid,serotonin,and glutamate)have been linked to alcoholism due to a brain imbalance.Alcoholism appears to be a complex genetic disorder,with variations in many genes influencing risk.Some of these genes have been identified,including two alcohol metabolism genes,alcohol dehydrogenase 1B gene and aldehyde dehydrogenase 2 gene,which have the most potent known effects on the risk of alcoholism.Neuronal degeneration and demyelination in people with AUD may be caused by neuronal damage,nutrient deficiencies,and blood brain barrier dysfunction;however,the underlying mechanism is unknown.This review will provide a detailed overview of the neurobiology of alcohol addiction,followed by recent studies published in the genetics of alcohol addiction,molecular mechanism and detailed information on the various acute and chronic neurological manifestations of alcoholism for the Future research.
基金supported by the 2024 Talent Project of Shandong First Medical University(045RC200008)the Taishan Scholars Program(tsqn202211225).
文摘Ferroptosis is a form of cell death elicited by an imbalance in intracellular iron concentrations,leading to enhanced lipid peroxidation.In neurological disorders,both oxidative stress and mitochondrial damage can contribute to ferroptosis,resulting in nerve cell dysfunction and death.The ubiquitin-proteasome system(UPS)refers to a cellular pathway in which specific proteins are tagged with ubiquitin for recognition and degradation by the proteasome.In neuro-logical conditions,the UPS plays a significant role in regu-lating ferroptosis.In this review,we outline how the UPS regulates iron metabolism,ferroptosis,and their interplay in neurological diseases.In addition,we discuss the future application of small-molecule inhibitors and identify poten-tial drug targets.Further investigation into the mechanisms of UPS-mediated ferroptosis will provide novel insights and strategies for therapeutic interventions and clinical applica-tions in neurological diseases.
基金supported by the National Natural Science Foundation of China,Nos.81901098(to TC),82201668(to HL)Fujian Provincial Health Technology Project,No.2021QNA072(to HL)。
文摘The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central nervous system, with sensory stimulation and excitation conduction functions. Astrocytes and microglia belong to the glial cell family, which is the main source of cytokines and represents the main defense system of the central nervous system. Nerve cells undergo neurotransmission or gliotransmission, which regulates neuronal activity via the ion channels, receptors, or transporters expressed on nerve cell membranes. Ion channels, composed of large transmembrane proteins, play crucial roles in maintaining nerve cell homeostasis. These channels are also important for control of the membrane potential and in the secretion of neurotransmitters. A variety of cellular functions and life activities, including functional regulation of the central nervous system, the generation and conduction of nerve excitation, the occurrence of receptor potential, heart pulsation, smooth muscle peristalsis, skeletal muscle contraction, and hormone secretion, are closely related to ion channels associated with passive transmembrane transport. Two types of ion channels in the central nervous system, potassium channels and calcium channels, are closely related to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Accordingly, various drugs that can affect these ion channels have been explored deeply to provide new directions for the treatment of these neurological disorders. In this review, we focus on the functions of potassium and calcium ion channels in different nerve cells and their involvement in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, epilepsy, autism, and rare disorders. We also describe several clinical drugs that target potassium or calcium channels in nerve cells and could be used to treat these disorders. We concluded that there are few clinical drugs that can improve the pathology these diseases by acting on potassium or calcium ions. Although a few novel ion-channelspecific modulators have been discovered, meaningful therapies have largely not yet been realized. The lack of target-specific drugs, their requirement to cross the blood–brain barrier, and their exact underlying mechanisms all need further attention. This review aims to explain the urgent problems that need research progress and provide comprehensive information aiming to arouse the research community's interest in the development of ion channel-targeting drugs and the identification of new therapeutic targets for that can increase the cure rate of nervous system diseases and reduce the occurrence of adverse reactions in other systems.
文摘BACKGROUND Artificial intelligence(AI)has become significantly integrated into healthcare,particularly in the diag-nosing of neurological disorders.This advancement has enabled neurologists and physicians to diagnose conditions more quickly and effectively,ultimately benefiting patients.AIM To explore the current status and key highlights of AI-related articles in diagnosing of neurological disorders.METHODS A systematic literature review was conducted in the Web of Science Core Collection database using the following strategy:TS=("Artificial Intelligence"OR"Computational Intelligence"OR"Machine Learning"OR"AI")AND TS=("Neurological disorders"OR"CNS disorder"AND"diagnosis").The search was limited to articles and reviews.Microsoft Excel 2019 and VOSviewer were utilized to identify major contributors,including authors,institutions,countries,and journals.Additionally,VOSviewer was employed to analyze and visualize current trends and hot topics through network visualization maps.RESULTS A total of 276 publications from 2000 to 2024 were retrieved.The United States,India,and China emerged as the top contributors in this field.Major institutions included Johns Hopkins University,King's College London,and Harvard Medical School.The most prolific author was U.Rajendra Acharya from the University of Southern Queensland(Australia).Among journals,IEEE Access,Scientific Reports,and Sensors were the most productive,while Frontiers in Neuroscience led in total citations.Central topics in AI-related articles on neurological disorders diagnosis included Alzheimer's disease,Parkinson's disease,dementia,epilepsy,autism,attention deficit hyperactivity disorder,and their intersections with deep learning and AI.CONCLUSION Research on AI's role in diagnosing neurological disorders is becoming widely recognized for its growing importance.AI shows promise in diagnosing various neurological disorders,yet requires further improvement and extensive future research.
基金supported by Warren Alpert Foundation and Houston Methodist Academic Institute Laboratory Operating Fund(to HLC).
文摘Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted therapies.To investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary time.Genetic tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological diseases.Drosophila boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug candidates.Researchers can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical trials.In this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic implications.We discuss rare diseases associated with both neuron-expressed and glial-expressed genes.Specific cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal movements.And we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell syndrome.Loss-of-function mutations in ACOX1 result in ACOX1 deficiency,characterized by very-long-chain fatty acid accumulation and glial degeneration.Notably,this review highlights how modeling these diseases in Drosophila has provided valuable insights into their pathophysiology,offering a platform for the rapid identification of potential therapeutic interventions.Rare neurological diseases involve a wide range of expression systems,and sometimes common phenotypes can be found among different genes that cause abnormalities in neurons or glia.Furthermore,mutations within the same gene may result in varying functional outcomes,such as complete loss of function,partial loss of function,or gain-of-function mutations.The phenotypes observed in patients can differ significantly,underscoring the complexity of these conditions.In conclusion,Drosophila represents an indispensable and cost-effective tool for investigating rare neurological diseases.By facilitating the modeling of these conditions,Drosophila contributes to a deeper understanding of their genetic basis,pathophysiology,and potential therapies.This approach accelerates the discovery of promising drug candidates,ultimately benefiting patients affected by these complex and understudied diseases.
文摘Perivascular space(PVS) is a crevice between two slices of cerebral pia maters,filled with tissue fluid,which be formed by pia mater emboling in the surrounding of cerebral perforating branch(excluding micrangium). Normal PVS(diameter < 2 mm) can be found in almost all healthy adults; however enlarged PVS(diameter > 2 mm) has correlation with neurological disorders probably. The article reviews the formation mechanism,imageology characteristics and the relation with neurological disorders of PVS,which...
文摘Extraintestinal manifestations occur in about one-third of patients living with inflammatory bowel disease(IBD) and may precede the onset of gastrointestinal symptoms by many years. Neurologic disorders associated with IBD are not frequent, being reported in 3% of patients, but they often represent an important cause of morbidity and a relevant diagnostic issue. In addition, the increasing use of immunosuppressant and biological therapies for IBD may also play a pivotal role in the development of neurological disorders of different type and pathogenesis. Hence, we provide a complete and profound review of the main features of neurological complications associated with IBD, with particular reference to those related to drugs and with a specific focus on their clinical presentation and possible pathophysiological mechanisms.
文摘Mesenchymal stem cells are multipotent cells that possess anti-inflammatory,antiapoptotic and immunomodulatory properties.The effects of existing drugs for neurodegenerative disorders such as Alzheimer’s disease are limited,thus mesenchymal stem cell therapy has been anticipated as a means of ameliorating neuronal dysfunction.Since mesenchymal stem cells are known to scarcely differentiate into neuronal cells in damaged brain after transplantation,paracrine factors secreted from mesenchymal stem cells have been suggested to exert therapeutic effects.Extracellular vesicles and exosomes are small vesicles released from mesenchymal stem cells that contain various molecules,including proteins,mRNAs and microRNAs.In recent years,administration of exosomes/extracellular vesicles in models of neurological disorders has been shown to improve neuronal dysfunctions,via exosomal transfer into damaged cells.In addition,various microRNAs derived from mesenchymal stem cells that regulate various genes and reduce neuropathological changes in various neurological disorders have been identified.This review summarizes the effects of exosomes/extracellular vesicles and exosomal microRNAs derived from mesenchymal stem cells on models of stroke,subarachnoid and intracerebral hemorrhage,traumatic brain injury,and cognitive impairments,including Alzheimer’s disease.
文摘Synapsins serve as flagships among the presynaptic proteins due to their abundance on synaptic vesicles and contribution to synaptic communication. Several studies have emphasized the importance of this multi-gene family of neuron-specific phosphoproteins in maintaining brain physiology. In the recent times, increasing evidence has established the relevance of alterations in synapsins as a major determinant in many neurological disorders. Here,we give a comprehensive description of the diverse roles of the synapsin family and the underlying molecular mechanisms that contribute to several neurological disorders.These physiologically important roles of synapsins associated with neurological disorders are just beginning to be understood. A detailed understanding of the diversified expression of synapsins may serve to strategize novel therapeutic approaches for these debilitating neurological disorders.
基金supported by the State Key Program of National Natural Science Foundation of China(31530056)the National First-class Discipline Program of Food Science and Technology(JUFSTR20180102)the Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province,China.
文摘It is well known that the gut microbiota plays an extremely important role in modulating host physiological functions such as immunity and metabolic homeostasis.In recent years,accumulated evidence has revealed that the gut microbiota can regulate the functions of the central nervous system(CNS)through the gut-brain axis,which provides a novel insight into the interactions between the gut and brain.This review focuses on the molecular mechanism of the crosstalk between the gut microbiota and the brain via the gut-brain axis,and on the onset and development of neurological disorders triggered by gut microbiota dysbiosis.These topics are followed by a critical analysis of potential intervention strategies targeting gut microbiota dysbiosis,including the use of probiotics,prebiotics,synbiotics,and diets.While research on the microbiota-gut-brain axis is still in its relative infancy,clarifying the molecular mechanism that underlies how the gut microbiota regulates neurological functions not only holds the promise of revealing potentially novel pathogeneses of neurological disorders,but also may lead to the development of potential diagnosis biomarkers and intervention strategies targeting microbiota dysbiosis for neurological disorders.
基金supported by the National Natural Science Foundation of China,No.31471044a grant from the Ministry of Science and Technology of China,No.2015AA020918
文摘Neurologic impairments are usually irreversible as a result of limited regeneration in the central nervous system.Therefore,based on the regenerative capacity of stem cells,transplantation therapies of various stem cells have been tested in basic research and preclinical trials,and some have shown great prospects.This manuscript overviews the cellular and molecular characteristics of embryonic stem cells,induced pluripotent stem cells,neural stem cells,retinal stem/progenitor cells,mesenchymal stem/stromal cells,and their derivatives in vivo and in vitro as sources for regenerative therapy.These cells have all been considered as candidates to treat several major neurological disorders and diseases,owing to their self-renewal capacity,multi-directional differentiation,neurotrophic properties,and immune modulation effects.We also review representative basic research and recent clinical trials using stem cells for neurodegenerative diseases,including Parkinson＇s disease,Alzheimer＇s disease,and age-related macular degeneration,as well as traumatic brain injury and glioblastoma.In spite of a few unsuccessful cases,risks of tumorigenicity,and ethical concerns,most results of animal experiments and clinical trials demonstrate efficacious therapeutic effects of stem cells in the treatment of nervous system disease.In summary,these emerging findings in regenerative medicine are likely to contribute to breakthroughs in the treatment of neurological disorders.Thus,stem cells are a promising candidate for the treatment of nervous system diseases.
基金Supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq),Funda o de AmparoàPesquisa do Estado de S o Paulo(FAPESP)and Instituto Nacional de Neurociência Translacional(INNT),Programa de Núcleos de Excelência(PRONEX)(Brazil)
文摘The kallikrein-kinin system(KKS) is an intricate endogenous pathway involved in several physiological and pathological cascades in the brain. Due to the pathological effects of kinins in blood vessels and tissues, their formation and degradation are tightly controlled. Their components have been related to several central nervous system diseases such as stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy and others. Bradykinin and its receptors(B1R and B2R) may have a role in the pathophysiology of certain central nervous system diseases. It has been suggested that kinin B1R is up-regulated in pathological conditions and has a neurodegenerative pattern, while kinin B2R is constitutive and can act as a neuroprotective factor in many neurological conditions. The renin angiotensin system(RAS) is an important blood pressure regulator and controls both sodium and water intake. AngⅡ is a potent vasoconstrictor molecule and angiotensin converting enzyme is the major enzyme responsible for its release. AngⅡ acts mainly on the AT1 receptor, with involvement in several systemic and neurological disorders. Brain RAS has been associated with physiological pathways, but is also associated with brain disorders. This review describes topics relating to the involvement of both systems in several forms of brain dysfunction and indicates components of the KKS and RAS that have been used as targets in several pharmacological approaches.
文摘Deep transcranial magnetic stimulation(DTMS)is a new non-invasive neuromodulation technique based on repetitive transcranial magnetic stimulation technology.The new H-coil has significant advantages in the treatment and mechanism research of psychiatric and neurological disorders.This is due to its deep stimulation site and wide range of action.This paper reviews the clinical progress of DTMS in psychiatric and neurological disorders such as Parkinson’s disease,Alzheimer’s disease,post-stroke motor dysfunction,aphasia,and other neurological disorders,as well as anxiety,depression,and schizophrenia.
基金the National Natural Science Foundation of China(Grant No.81102401).
文摘Although therapeutic potential of neurotrophic factors(NTFs)has been well recognized for over two decades,attempts to translate that potential to the clinic have been disappointing,largely due to significant obstacles in delivery,including inadequate protein dose/kinetics released at target sites.Considerable efforts have been made to improve the therapeutic performance of NTFs.This articles reviews recent developments in localized delivery systems of NTFs for the neurological disorders treatments with a main focus on sustained delivery strategies.Different non-covalent binding approaches have been employed to immobilize proteins in hydrogels,microspheres,electrospun nanofibers,and their combined systems,which serve as depots for sustained local release of NTFs.The challenges associated with current NTFs delivery systems and how these systems can be applied to neurological diseases and disorders have been discussed in the review.In conclusion,optimal delivery systems for NTFs will be needed for reliable and meaningful clinical benefits;ideally,delivering a time and dose-controlled release of bioactive multiNTFs at different individual optimal kinetics to achieve multi-functions in target tissues is significant preferred.
文摘Background and object:The burden of neurological disorders in India is expected to increase due to the rapid demographic and epidemiological transition,with irrational drug use,which is also a global concern.Thus,drug utilization evaluation is designed to ensure appropriate medicine use within the healthcare settings.The aim of the study was to assess the rate and pattern of drug utilization in the management of neurological disorders.Materials and methods:A hospital-based cross-sectional drug utilization evaluation study on neurological drugs was carried out at the Department of Neurology over a span of six months.All legible prescriptions consisting neurological medications irrespective of patient's gender,aged≥18 years were included for the study.The World Health Organization(WHO)core drug use indicators were used to assess the drug prescribing and utilization patterns.Results:A total of 310 prescriptions were reviewed,where male predominance was found to be 56.45%.Out of 310 prescriptions,drugs belonging to 26 neurological classes were prescribed for the management of various neurological disorders.The majority of patients were diagnosed with epilepsy and the most prescribed drugs per patient were phenytoin(14.8%)and valproic acid(6.45%).By following the WHO core drug prescribing indicators,65.47%of drugs prescribed from the India National List of Essential Medicines,2022,followed by 29.83%of drugs prescribed in generic name and 10.86%of prescriptions including injections.Conclusion:The study findings showed that the prescribing pattern in the Department of Neurology was in accordance with the WHO core prescribing indicators.But,the extent of polypharmacy prescriptions was very high.Therefore,interventions are very necessary to promote rational drug prescribing patterns and thus clinical pharmacists can contribute to assess and review the drug utilization pattern to optimize the drug therapy and improvement in patient safety.
文摘Several diseases have been successfully modeled since the development of induced pluripotent stem cell(i PSC) technology in 2006. Since then, methods for increased reprogramming efficiency and cell culture maintenance have been optimized and many protocols for differentiating stem cell lines have been successfully developed, allowing the generation of several cellular subtypes in vitro. Gene editing technologies have also greatly advanced lately, enhancing disease-specific phenotypes by creating isogenic cell lines, allowing mutations to be corrected in affected samples or inserted in control lines. Neurological disorders have benefited the most from i PSC-disease modeling for its capability for generating disease-relevant cell types in vitro from the central nervous system, such as neurons and glial cells, otherwise only available from post-mortem samples. Patient-specific i PSC-derived neural cells can recapitulate the phenotypes of these diseases and therefore, considerably enrich our understanding of pathogenesis, disease mechanism and facilitate the development of drug screening platforms for novel therapeutic targets. Here, we review the accomplishments and the current progress in human neurological disorders by using i PSC modeling for Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal muscular atrophy, amyotrophic lateral sclerosis, duchenne muscular dystrophy, schizophrenia and autism spectrum disorders, which include Timothy syndrome, Fragile X syndrome, Angelman syndrome, Prader-Willi syndrome, PhelanMc Dermid, Rett syndrome as well as Nonsyndromic Autism.
基金supported by Cátedra Marcos Moshinsky (to EM)CONACyT Fronteras de la Ciencia#536 (to EM)+1 种基金VIEP-PIFI-FOMES-PROMEP-BUAP-Puebla (to EM)Comitéde Internacionalización de la Investigación (to EM),México
文摘Random noise stimulation technique involves applying any form of energy(for instance,light,mechanical,electrical,sound)with unpredictable intensities through time to the brain or sensory receptors to enhance sensory,motor,or cognitive functions.Random noise stimulation initially employed mechanical noise in auditory and cutaneous stimuli,but electrical energies applied to the brain or the skin are becoming more frequent,with a series of clinical applications.Indeed,recent evidence shows that transcranial random noise stimulation can increase corticospinal excitability,improve cognitive/motor performance,and produce beneficial aftereffects at the behavioral and psychological levels.Here,we present a narrative review about the potential uses of random noise stimulation to treat neurological disorders,including attention deficit hyperactivity disorder,schizophrenia,amblyopia,myopia,tinnitus,multiple sclerosis,post-stroke,vestibular-postural disorders,and sensitivity loss.Many of the reviewed studies reveal that the optimal way to deliver random noise stimulation-based therapies is with the concomitant use of neurological and neuropsychological assessments to validate the beneficial aftereffects.In addition,we highlight the requirement of more randomized controlled trials and more physiological studies of random noise stimulation to discover another optimal way to perform the random noise stimulation interventions.
文摘Neurological disorders are amongst the most widely studied human aliments.Yet,they are also one of the most poorly understood.Although most of these disorders are polygenic,genotype still plays an important role in their etiologies.For example,in schizophrenia and autism spectrum disorders,there is a 40-60%concordance rate in monozygotic twins,with 60-90%heritability（Burmeister et al.,2008）.However,the mechanisms by which multiple genes and their genomic variations influence the phenotypes of the disorders remain to be understood. The complexities of the disorders are tur- ther compounded by the individual rarity of the genomic variations and their variable penetrance （Cook and Scherer, 2008）. Thus, conventional disease modeling, such as gene knockout in cells or in animals, to attain the desired disease genotype may not be the most suitable platform for tackling most neurological disorders.
文摘This review reflects upon our own as well as other investigators’studies on the role of receptor for advanced glycation end-products(RAGE),bringing up the latest information on RAGE in physiology and pathology of the nervous system.Over the last ten years,major progress has been made in uncovering many of RAGE-ligand interactions and signaling pathways in nervous tissue;however,the translation of these discoveries into clinical practice has not come to fruition yet.This is likely,in part to be the result of our incomplete understanding of this crucial signaling pathway.Clinical trials examining the therapeutic efficacy of blocking RAGE-external ligand interactions by genetically engineered soluble RAGE or an endogenous RAGE antagonist,has not stood up to its promise;however,other trials with different blocking agents are being considered with hope for therapeutic success in diseases of the nervous system.
文摘The central nervous system(CNS)is a reservoir of immune privilege.Specialized immune glial cells are responsible for maintenance and defense against foreign invaders.The blood–brain barrier(BBB)prevents detrimental pathogens and potentially overreactive immune cells from entering the periphery.When the double-edged neuroinflammatory response is overloaded,it no longer has the protective function of promoting neuroregeneration.Notably,microbiota and its derivatives may emerge as pathogen-associated molecular patterns of brain pathology,causing microbiome–gut–brain axis dysregulation from the bottom-up.When dysbiosis of the gastrointestinal flora leads to subsequent alterations in BBB permeability,peripheral immune cells are recruited to the brain.This results in amplification of neuroinflammatory circuits in the brain,which eventually leads to specific neurological disorders.Aggressive treatment strategies for gastrointestinal disorders may protect against specific immune responses to gastrointestinal disorders,which can lead to potential protective effects in the CNS.Accordingly,this study investigated the mutual effects of microbiota and the gut–brain axis,which may provide targeting strategies for future disease treatment.
