Prions are infectious conformations of certain naturally occurring proteins.These misfolded proteins can structurally alter healthy protein,creating misfolded copies that repeat the process and form protein aggr...Prions are infectious conformations of certain naturally occurring proteins.These misfolded proteins can structurally alter healthy protein,creating misfolded copies that repeat the process and form protein aggregates that lead to neuronal cell death.Although years can pass from initial prion infection to clinical presentation of symptoms,onset of symptoms is typically followed by rapid neurological decline resulting in death.Prion diseases have been characterized in animals ranging from sheep and cattle to cervids and humans,with notable cross-species infections such as the variant Creutzfeldt-Jakob disease.Thus,prions present a health risk with the potential to disrupt major food sources as well affect human health through animal to human and human to human transmission events.While human to human prion transmission is rare and the immediate risks for a prion-facilitated pandemic are low,prions are a class of pathogens for which we are underprepared.In addition,prions,and prion disease-like approaches,have also been discussed in the context of biological weapons and toxins,adding another layer of complexity surrounding biosecurity and biodefense.These threats underscore the need for increased scrutiny and research on prions.Here,pharmaceutical and nonpharmaceutical prion-specific interventions are discussed.Recent advances in prion therapeutic development are also briefly highlighted,and a set of policy recommendations are given that aims to provide high level suggestions for the prevention and mitigation of prion diseases.展开更多
We investigated the role of hydrological features, such as water masses, fronts, eddies, and sea ice, in affecting the distribution of upper trophic level species in the Scotia Sea region during autumn. On board RV Po...We investigated the role of hydrological features, such as water masses, fronts, eddies, and sea ice, in affecting the distribution of upper trophic level species in the Scotia Sea region during autumn. On board RV Polarstern, we performed 365 30-min strip transects recording seabirds and marine mammals along the North Scotia Ridge and the South Sandwich Trench in March--April 2013. Among the 7 identified cetacean species recorded, the humpback whale Megaptera novaeangliae was the most abundant baleen whale （40 individuals）, and noteworthy were sightings of six southern right whales Eubalaena australis. Pinnipeds （3 species, 1650 individuals） were dominated by Antarctic fur seal Arctocephalus gazella （99%）, and seabirds （36 species, 18900 individuals） by Antarctic prion Pachyptila desolata （-50%）. The distribution of these top predators was highly patchy with the majority of observations concentrated in a few counts. This heterogeneity is likely a result of prey availability, and we discuss how hydrological features may have caused the patchiness.展开更多
Proteinaceous infectious particles(prions) are unique pathogens as they are devoid of any coding nucleic acid.Whilst it is assumed that prion disease is transmitted by a misfolded isoform of the cellular prion protein...Proteinaceous infectious particles(prions) are unique pathogens as they are devoid of any coding nucleic acid.Whilst it is assumed that prion disease is transmitted by a misfolded isoform of the cellular prion protein, the structural insight of prions is still vague and research for high resolution structural information of prions is still ongoing. In this review, techniques that may contribute to the clarification of the conformation of prions are presented and discussed.展开更多
PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other mammals.PrPSccan adopt different patho...PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other mammals.PrPSccan adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective therapies.Since PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion diseases.In this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of action.We argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.展开更多
BACKGROUND The cellular prion protein(PrPC),traditionally associated with neurodegenerative disorders,plays an important role in cancer progression and metastasis by inhibiting apoptosis.AIM To investigate the influen...BACKGROUND The cellular prion protein(PrPC),traditionally associated with neurodegenerative disorders,plays an important role in cancer progression and metastasis by inhibiting apoptosis.AIM To investigate the influence of PrPC expression in cholangiocarcinoma(CCA)on patient outcomes following surgical resection.METHODS Patients who underwent curative surgical resection for either intrahepatic or hilar CCA were enrolled in this retrospective study.Based on the immunohistochemical staining results of the surgical specimens,patients were categorized into two groups:The low PrPC group(negative or 1+)and the high PrPC group(2+or 3+).Survival analyses,including overall survival and recurrence-free survival,were conducted using the Kaplan-Meier method and compared using the log-rank test.RESULTS In total,seventy-six patients diagnosed with CCA(39 with intrahepatic and 37 with hilar CCA)underwent curative hepatectomy from January 2011 to November 2021.Among these patients,38(50%)demonstrated high PrPC expression,whereas the remaining 38(50%)showed low expression of PrPC.During a median follow-up period of 31.2 months(range:1 to 137 months),the high PrPC group had a significantly shorter median overall survival than the low PrPC group(40.4 months vs 137.9 months,respectively;P=0.041).Moreover,the high PrPC group had a significantly shorter median recurrence-free survival than the low PrPC group(13.3 months vs 23.8 months,respectively;P=0.026).CONCLUSION PrPC expression is significantly associated with early recurrence and decreased survival period in CCA patients following surgical resection.Thus,PrPC may be used as a prognostic factor in treatment planning.展开更多
Background:Prion diseases(PrDs)are fatal transmissible neurodegenerative disorders caused by misfolded prion protein,which is highly expressed in the brain.Drosophila has been employed as a model system for studying m...Background:Prion diseases(PrDs)are fatal transmissible neurodegenerative disorders caused by misfolded prion protein,which is highly expressed in the brain.Drosophila has been employed as a model system for studying mammalian neurodegenerative diseases.Methods:Drosophila transgenic for hamster prion protein(HaPrP)was generated by Valium20 transformation.Locomotion,longevity,protease resistance,and histology were assessed,and nontargeted metabolomics analyses were performed to investigate the changes in Drosophila metabolism with the HaPrP expression and metformin treatment.Results:The Drosophila model exhibited pan-neuronal expression of HaPrP,with expression levels increasing with age.Flies displayed reduced climbing ability,shortened lifespan,and vacuolar structures in the brain.Additionally,HaPrP expressed in older flies demonstrated resistance to digestion by 5μg/mL Proteinase K.The Drosophila model also displayed alterations in protein,lipid,and carbohydrate metabolism.We hypothesize that glutamate,N-acetylaspartate,ceramide,phosphatidylethanolamine,dihydroxyacetone phosphate,ribose-5-phosphate,and pyruvate are key metabolites potentially related to PrDs.Metformin improved locomotor activity,reduced PrP res formation,and ameliorated mitochondrial dysfunction in flies,which may be associated with alterations in succinate,pyruvate,choline,and sphingomyelin levels.Conclusions:We generated a Drosophila model of PrDs that recapitulates key pathological features observed in mammals.Preliminary applications have demonstrated that the Drosophila model is suitable for PrDs research and the highthroughput screening of potential therapeutic compounds.展开更多
Parkinson's disease(PD)is a neurodegenerative disorder characterized byα-Synuclein(α-Syn)aggregation and dopaminergic neuron degeneration[1].While traditionally considered a central nervous system(CNS)disorder,g...Parkinson's disease(PD)is a neurodegenerative disorder characterized byα-Synuclein(α-Syn)aggregation and dopaminergic neuron degeneration[1].While traditionally considered a central nervous system(CNS)disorder,growing evidence suggestsα-Syn pathology in the peripheral organs such as skin,minor salivary glands,submandibular glands,and so on[1].Recent studies have primarily focused on the gastrointestinal tract,supporting the hypothesis thatα-Syn may propagate from the gut to the brain in a prion-like manner[2,3].However,in a groundbreaking study published in Nature Neuroscience,Xin Yuan et al.have provided a novel perspective on the peripheral origins of PD,revealing for the first time the critical role of the kidney in the pathological transmission and initiation ofα-Syn(Fig.1)[4].展开更多
Objective:The World Health Organization(WHO)grading based on histopathology cannot always accurately predict tumor behavior of meningiomas.To overcome the limitations of the WHO grading,the study aims to propose a nov...Objective:The World Health Organization(WHO)grading based on histopathology cannot always accurately predict tumor behavior of meningiomas.To overcome the limitations of the WHO grading,the study aims to propose a novel oxidative stress-based molecular classification for WHO grade 2/3 meningiomas.Methods:Differentially expressed oxidative stress-related genes were analyzed between 86 WHO grade 1(low grade)meningiomas and 99 grade 2/3(high grade)meningiomas.An oxidative stress-based molecular classification was developed in high-grade meningiomas through consensus clustering analysis.Immune microenvironment features,responses to immunotherapy and chemotherapy,and targeted drugs were evaluated.Three machine learning models:logistic regression,support vector machine,and random forest,were built for differentiating the classification.Key oxidative stress-related geneswere verified in humanmeningeal cells(HMC)and two meningioma cells(CH-157MN and IOMMLee)via reverse transcription quantitative polymerase chain reaction(RT-qPCR)and western blot.After knockdown of Forkhead Box M1(FOXM1)or Prion Protein(PRNP),cell growth,migration,and reactive oxygen species(ROS)levels were measured through cell counting kit-8(CCK-8),transwell,and immunofluorescence,respectively.Results:We classified high-grade meningiomas into two oxidative stress-based clusters,termed cluster 1 and cluster 2.Cluster 1 exhibited higher infiltrations of immune and stromal cells and higher expression of classic immune checkpoints:Cluster of Differentiation 86(CD86),Programmed Cell Death 1(PDCD1),and Leukocyte-Associated Immunoglobulin-Like Receptor 1(LAIR1),indicating that cluster 1 meningiomas might respond to immunotherapy.Drug sensitivity was heterogeneous between the two clusters.Three classifiers were established,which could accurately differentiate this molecular classification.FOXM1 and PRNP were experimentally evidenced to be highly expressed inmeningioma cells,and their knockdown hindered cell growth and migration and triggered ROS accumulation.Conclusion:In summary,our findings established a novel oxidative stress-based molecular classification and identified potential treatment vulnerabilities in high-grade meningiomas,which might assist personalized clinical management.展开更多
Parkinson's disease(PD)is the second most prevalent neurodegenerative disorder after Alzheimer's disease(AD),and currently,no disease-modifying therapies are available[1].A key pathological hallmark of PD is t...Parkinson's disease(PD)is the second most prevalent neurodegenerative disorder after Alzheimer's disease(AD),and currently,no disease-modifying therapies are available[1].A key pathological hallmark of PD is the presence of Lewy bodies,which are primarily composed of aggregatedα-synuclein(α-syn)[2].The misfolding,self-aggregation,and inter-neuronal propagation of pathologicalα-syn,likely via a prion-like mechanism,are thought to drive the progressive degeneration of dopaminergic neurons and contribute to disease progression[3].However,the molecular mechanisms governing the neuronal uptake and inter-neuronal transmission ofα-syn remain inadequately understood.展开更多
Neuron glia antigen-2(NG2)glia,also known as oligodendrocyte precursor cells(OPCs),are essential for maintaining the normal function and structure of the central nervous system(CNS)due to their supportive role[1].Unde...Neuron glia antigen-2(NG2)glia,also known as oligodendrocyte precursor cells(OPCs),are essential for maintaining the normal function and structure of the central nervous system(CNS)due to their supportive role[1].Under physiological conditions,NG2 glia are involved in myelination by differentiating into oligodendrocytes,which are responsible for forming the myelin sheath around axons[2].In addition,the NG2 glia can directly influence the activity of neuronal circuits by receiving synaptic input from neurons and generating action potentials[3].Under pathological conditions,such as in response to injury or disease,the NG2 glia proliferate and differentiate to replace damaged oligodendrocytes,contributing to the repair and regeneration of myelin[4].展开更多
羊痒病(scrap ie)是传染性海绵状脑病(TSE)的原型,目前在世界许多地方流行。该病是绵羊的一种缓慢发展的致死性中枢神经系统变性疾病,能引起绵羊和山羊中枢神经系统发生退化变性,病羊具有中枢神经系统变性、空泡化、星形胶质细胞增生等...羊痒病(scrap ie)是传染性海绵状脑病(TSE)的原型,目前在世界许多地方流行。该病是绵羊的一种缓慢发展的致死性中枢神经系统变性疾病,能引起绵羊和山羊中枢神经系统发生退化变性,病羊具有中枢神经系统变性、空泡化、星形胶质细胞增生等特点,病羊表现为共济失调、痉挛、麻痹、衰弱和严重的皮肤瘙痒,病畜死亡率达100%。该病是由正常的朊蛋白(P rP c)发生错误折叠而变成异常的蛋白形式(P rP sc)引起的。展开更多
文摘Prions are infectious conformations of certain naturally occurring proteins.These misfolded proteins can structurally alter healthy protein,creating misfolded copies that repeat the process and form protein aggregates that lead to neuronal cell death.Although years can pass from initial prion infection to clinical presentation of symptoms,onset of symptoms is typically followed by rapid neurological decline resulting in death.Prion diseases have been characterized in animals ranging from sheep and cattle to cervids and humans,with notable cross-species infections such as the variant Creutzfeldt-Jakob disease.Thus,prions present a health risk with the potential to disrupt major food sources as well affect human health through animal to human and human to human transmission events.While human to human prion transmission is rare and the immediate risks for a prion-facilitated pandemic are low,prions are a class of pathogens for which we are underprepared.In addition,prions,and prion disease-like approaches,have also been discussed in the context of biological weapons and toxins,adding another layer of complexity surrounding biosecurity and biodefense.These threats underscore the need for increased scrutiny and research on prions.Here,pharmaceutical and nonpharmaceutical prion-specific interventions are discussed.Recent advances in prion therapeutic development are also briefly highlighted,and a set of policy recommendations are given that aims to provide high level suggestions for the prevention and mitigation of prion diseases.
文摘We investigated the role of hydrological features, such as water masses, fronts, eddies, and sea ice, in affecting the distribution of upper trophic level species in the Scotia Sea region during autumn. On board RV Polarstern, we performed 365 30-min strip transects recording seabirds and marine mammals along the North Scotia Ridge and the South Sandwich Trench in March--April 2013. Among the 7 identified cetacean species recorded, the humpback whale Megaptera novaeangliae was the most abundant baleen whale （40 individuals）, and noteworthy were sightings of six southern right whales Eubalaena australis. Pinnipeds （3 species, 1650 individuals） were dominated by Antarctic fur seal Arctocephalus gazella （99%）, and seabirds （36 species, 18900 individuals） by Antarctic prion Pachyptila desolata （-50%）. The distribution of these top predators was highly patchy with the majority of observations concentrated in a few counts. This heterogeneity is likely a result of prey availability, and we discuss how hydrological features may have caused the patchiness.
基金Supported by Alberta Prion Research Institute,Canada(Project title:"Comprehensive Risk Assessment of CWD Transmission to Humans Using Non-human Primates")European Metrology Research Programme(EMRP)Researcher Grant:HLT10-Bi Origin(Metrology for the Biomolecular Origin of Disease)
文摘Proteinaceous infectious particles(prions) are unique pathogens as they are devoid of any coding nucleic acid.Whilst it is assumed that prion disease is transmitted by a misfolded isoform of the cellular prion protein, the structural insight of prions is still vague and research for high resolution structural information of prions is still ongoing. In this review, techniques that may contribute to the clarification of the conformation of prions are presented and discussed.
基金supported by a grant from NIH(R01AI132695)to RM。
文摘Chronic wasting disease—a prion disease affecting cervids:Many neurological conditions,including Alzheimer's and Parkinson's diseases,amyotrophic lateral sclerosis,frontotemporal dementias,among others,are caused by the accumulation of misfolded proteins in the brain.These diseases affect not only humans,but also animals.
基金supported by Telethon Italy award GGP15225(to RC and GM)Italian Ministry of Health award RF-2016-02362950(to RC and CZ)+1 种基金the CJD Foundation USA(to RC)the Associazione Italiana Encefalopatie da Prioni(AIEnP)(to RC).
文摘PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other mammals.PrPSccan adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective therapies.Since PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion diseases.In this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of action.We argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.
基金Supported by National Research Foundation of Korea Grant Funded by the Korea Government,No.RS-2023-00213951.
文摘BACKGROUND The cellular prion protein(PrPC),traditionally associated with neurodegenerative disorders,plays an important role in cancer progression and metastasis by inhibiting apoptosis.AIM To investigate the influence of PrPC expression in cholangiocarcinoma(CCA)on patient outcomes following surgical resection.METHODS Patients who underwent curative surgical resection for either intrahepatic or hilar CCA were enrolled in this retrospective study.Based on the immunohistochemical staining results of the surgical specimens,patients were categorized into two groups:The low PrPC group(negative or 1+)and the high PrPC group(2+or 3+).Survival analyses,including overall survival and recurrence-free survival,were conducted using the Kaplan-Meier method and compared using the log-rank test.RESULTS In total,seventy-six patients diagnosed with CCA(39 with intrahepatic and 37 with hilar CCA)underwent curative hepatectomy from January 2011 to November 2021.Among these patients,38(50%)demonstrated high PrPC expression,whereas the remaining 38(50%)showed low expression of PrPC.During a median follow-up period of 31.2 months(range:1 to 137 months),the high PrPC group had a significantly shorter median overall survival than the low PrPC group(40.4 months vs 137.9 months,respectively;P=0.041).Moreover,the high PrPC group had a significantly shorter median recurrence-free survival than the low PrPC group(13.3 months vs 23.8 months,respectively;P=0.026).CONCLUSION PrPC expression is significantly associated with early recurrence and decreased survival period in CCA patients following surgical resection.Thus,PrPC may be used as a prognostic factor in treatment planning.
基金National Key Research and Development Program,Grant/Award Number:2022YFD1800505Hainan Province Science and Technology Special Fund,Grant/Award Number:ZDYF2024XDNY198+1 种基金Beijing Municipal Natural Science Foundation,Grant/Award Number:6232025Natural Science Foundation of China,Grant/Award Number:32272960。
文摘Background:Prion diseases(PrDs)are fatal transmissible neurodegenerative disorders caused by misfolded prion protein,which is highly expressed in the brain.Drosophila has been employed as a model system for studying mammalian neurodegenerative diseases.Methods:Drosophila transgenic for hamster prion protein(HaPrP)was generated by Valium20 transformation.Locomotion,longevity,protease resistance,and histology were assessed,and nontargeted metabolomics analyses were performed to investigate the changes in Drosophila metabolism with the HaPrP expression and metformin treatment.Results:The Drosophila model exhibited pan-neuronal expression of HaPrP,with expression levels increasing with age.Flies displayed reduced climbing ability,shortened lifespan,and vacuolar structures in the brain.Additionally,HaPrP expressed in older flies demonstrated resistance to digestion by 5μg/mL Proteinase K.The Drosophila model also displayed alterations in protein,lipid,and carbohydrate metabolism.We hypothesize that glutamate,N-acetylaspartate,ceramide,phosphatidylethanolamine,dihydroxyacetone phosphate,ribose-5-phosphate,and pyruvate are key metabolites potentially related to PrDs.Metformin improved locomotor activity,reduced PrP res formation,and ameliorated mitochondrial dysfunction in flies,which may be associated with alterations in succinate,pyruvate,choline,and sphingomyelin levels.Conclusions:We generated a Drosophila model of PrDs that recapitulates key pathological features observed in mammals.Preliminary applications have demonstrated that the Drosophila model is suitable for PrDs research and the highthroughput screening of potential therapeutic compounds.
基金supported by the Science,Technology,and Development Foundation of Wuxi City(Y20222026)Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(SJCX25_0136).
文摘Parkinson's disease(PD)is a neurodegenerative disorder characterized byα-Synuclein(α-Syn)aggregation and dopaminergic neuron degeneration[1].While traditionally considered a central nervous system(CNS)disorder,growing evidence suggestsα-Syn pathology in the peripheral organs such as skin,minor salivary glands,submandibular glands,and so on[1].Recent studies have primarily focused on the gastrointestinal tract,supporting the hypothesis thatα-Syn may propagate from the gut to the brain in a prion-like manner[2,3].However,in a groundbreaking study published in Nature Neuroscience,Xin Yuan et al.have provided a novel perspective on the peripheral origins of PD,revealing for the first time the critical role of the kidney in the pathological transmission and initiation ofα-Syn(Fig.1)[4].
基金supported by Hubei Provincial Natural Science Foundation of China(grants 2023AFB208)the Chinese Primary Health Care Foundation(Grant No.cphcf-2022-222)+2 种基金2025 Hubei Provincial Natural Science Foundation Innovation and Development Joint Fund Project:(JCZRLH202500457)Shanghai Foundation for Anti-Cancer&Cancer Prevention Development Phase II Exploration Oncology Research Fund Project:“Study on the Mechanism of ANO9-Mediated Cetuximab Resistance in Head and Neck Squamous Cell Carcinoma”(No Grant Number)Qingdao Sheci Public Welfare Relief Center Pan-Cancer Treatment Research Fund Project:(QD-HN30008).
文摘Objective:The World Health Organization(WHO)grading based on histopathology cannot always accurately predict tumor behavior of meningiomas.To overcome the limitations of the WHO grading,the study aims to propose a novel oxidative stress-based molecular classification for WHO grade 2/3 meningiomas.Methods:Differentially expressed oxidative stress-related genes were analyzed between 86 WHO grade 1(low grade)meningiomas and 99 grade 2/3(high grade)meningiomas.An oxidative stress-based molecular classification was developed in high-grade meningiomas through consensus clustering analysis.Immune microenvironment features,responses to immunotherapy and chemotherapy,and targeted drugs were evaluated.Three machine learning models:logistic regression,support vector machine,and random forest,were built for differentiating the classification.Key oxidative stress-related geneswere verified in humanmeningeal cells(HMC)and two meningioma cells(CH-157MN and IOMMLee)via reverse transcription quantitative polymerase chain reaction(RT-qPCR)and western blot.After knockdown of Forkhead Box M1(FOXM1)or Prion Protein(PRNP),cell growth,migration,and reactive oxygen species(ROS)levels were measured through cell counting kit-8(CCK-8),transwell,and immunofluorescence,respectively.Results:We classified high-grade meningiomas into two oxidative stress-based clusters,termed cluster 1 and cluster 2.Cluster 1 exhibited higher infiltrations of immune and stromal cells and higher expression of classic immune checkpoints:Cluster of Differentiation 86(CD86),Programmed Cell Death 1(PDCD1),and Leukocyte-Associated Immunoglobulin-Like Receptor 1(LAIR1),indicating that cluster 1 meningiomas might respond to immunotherapy.Drug sensitivity was heterogeneous between the two clusters.Three classifiers were established,which could accurately differentiate this molecular classification.FOXM1 and PRNP were experimentally evidenced to be highly expressed inmeningioma cells,and their knockdown hindered cell growth and migration and triggered ROS accumulation.Conclusion:In summary,our findings established a novel oxidative stress-based molecular classification and identified potential treatment vulnerabilities in high-grade meningiomas,which might assist personalized clinical management.
基金supported by the Natural Science Foundation of Liaoning Province,China(2023-MSLH-029).
文摘Parkinson's disease(PD)is the second most prevalent neurodegenerative disorder after Alzheimer's disease(AD),and currently,no disease-modifying therapies are available[1].A key pathological hallmark of PD is the presence of Lewy bodies,which are primarily composed of aggregatedα-synuclein(α-syn)[2].The misfolding,self-aggregation,and inter-neuronal propagation of pathologicalα-syn,likely via a prion-like mechanism,are thought to drive the progressive degeneration of dopaminergic neurons and contribute to disease progression[3].However,the molecular mechanisms governing the neuronal uptake and inter-neuronal transmission ofα-syn remain inadequately understood.
基金supported by the National Natural Science Foundation of China(32300959)a Guangzhou Scientific Research Grant(SL2024A04J00578)the SCNU Young Faculty Development Program(22KJ04).
文摘Neuron glia antigen-2(NG2)glia,also known as oligodendrocyte precursor cells(OPCs),are essential for maintaining the normal function and structure of the central nervous system(CNS)due to their supportive role[1].Under physiological conditions,NG2 glia are involved in myelination by differentiating into oligodendrocytes,which are responsible for forming the myelin sheath around axons[2].In addition,the NG2 glia can directly influence the activity of neuronal circuits by receiving synaptic input from neurons and generating action potentials[3].Under pathological conditions,such as in response to injury or disease,the NG2 glia proliferate and differentiate to replace damaged oligodendrocytes,contributing to the repair and regeneration of myelin[4].
文摘羊痒病(scrap ie)是传染性海绵状脑病(TSE)的原型,目前在世界许多地方流行。该病是绵羊的一种缓慢发展的致死性中枢神经系统变性疾病,能引起绵羊和山羊中枢神经系统发生退化变性,病羊具有中枢神经系统变性、空泡化、星形胶质细胞增生等特点,病羊表现为共济失调、痉挛、麻痹、衰弱和严重的皮肤瘙痒,病畜死亡率达100%。该病是由正常的朊蛋白(P rP c)发生错误折叠而变成异常的蛋白形式(P rP sc)引起的。
