Neurodegenerative diseases(NDs)are a major threat to the elderly,and efficient therapy is rarely available.A group of phytochemicals has been shown to ameliorate NDs;however,poor stability,low bioavailability,and redu...Neurodegenerative diseases(NDs)are a major threat to the elderly,and efficient therapy is rarely available.A group of phytochemicals has been shown to ameliorate NDs;however,poor stability,low bioavailability,and reduced drug accumulation in brain tissue limit their application in NDs.Therefore,a targeted drug delivery system is a feasible treatment strategy for NDs.Extracellular vesicles(EVs)possess many favorable bioactivities and are excellent carriers for targeting brain tissue.This review summarizes EVs as novel phytochemical carriers in ND therapy.First,we discuss the current challenges of ND therapy and the therapeutic effects of phytochemicals for NDs.Second,we highlight the ability of EVs to cross the blood-brain barrier and act as drug carriers to enhance the therapeutic efficacy of drugs for NDs.Finally,encapsulation strategies for phytochemicals in EVs are particularly reviewed,as they are critical for obtaining high loading efficacy and stable drug delivery systems.This review provides new insights into EV-based drug delivery systems for improving the therapeutic effect of phytochemicals for ND treatment.Therefore,the release rate and pharmacokinetics of phytochemicals should be well controlled to ensure the therapeutic efficacy of phytochemical-loaded EVs in the brain.展开更多
Polyglutamine （polyQ） diseases are a family of neurodegenerative disorders including Huntington’s disease, spinobulbar muscular atrophy,dentatorubral-pallidoluysian atrophy and several spinocerebellar ataxias.polyQ...Polyglutamine （polyQ） diseases are a family of neurodegenerative disorders including Huntington’s disease, spinobulbar muscular atrophy,dentatorubral-pallidoluysian atrophy and several spinocerebellar ataxias.polyQ diseases are caused by abnormal expansion of CAG repeats in certain genes.The expanded CAG repeats are then translated into a series of abnormally expanded polyQ tracts.Such polyQ tracts may induce misfolding of the disease-causing proteins.The present review mainly focuses on the common characteristics of the pathogenesis of these polyQ diseases,including conformational transition of proteins and its influence on the function of these proteins,the correlation between decreased ability of proteoly-sis and late-onset polyQ diseases,and the relationship between wide expression of disease-causing proteins and selective neuronal death.展开更多
Wnts comprise a large family of proteins that have shown to be part of a signaling cascade that regulates several aspects of develop- ment including organogenesis, mid brain development as welt as stem cell proliferat...Wnts comprise a large family of proteins that have shown to be part of a signaling cascade that regulates several aspects of develop- ment including organogenesis, mid brain development as welt as stem cell proliferation. Wnt signaling pathway plays different roles in the development of neuronal circuits and also in the adult brain, where it regulates synaptic transmission and plasticity. It has been also implicated in various diseases including cancer and neurodegenerative diseases, reflecting its relevance in fundamental biological pro- cesses. This review summarizes the progress about Wnts function in mature nervous system with a focus on Alzheimer＇s disease （AD）. We discuss the prospects of modulating canonical and non-canonical Wnt signaling as a strategy for neuroprotection. This will include the potential of Wnts to： （i） act as potent regulators of hippocampai synapses and impact in learning and memory; （ii） regulate adult neurogenesis; and finally （iii） control AD pathogenesis.展开更多
Multiple sclerosis(MS) is an autoimmune disease of the central nervous system(CNS), with focal T lymphocytic infiltration and damage of myelin and axons. The underlying mechanism of pathogenesis remains unclear and th...Multiple sclerosis(MS) is an autoimmune disease of the central nervous system(CNS), with focal T lymphocytic infiltration and damage of myelin and axons. The underlying mechanism of pathogenesis remains unclear and there are currently no effective treatments. The development of neural stem cell(NSC) transplantation provides a promising strategy to treat neurodegenerative disease. However, the limited availability of NSCs prevents their application in neural disease therapy. In this study, we generated NSCs from induced pluripotent stem cells(iPSCs) and transplanted these cells into mice with experimental autoimmune encephalomyelitis(EAE), a model of MS. The results showed that transplantation of iPSC-derived NSCs dramatically reduced T cell infiltration and ameliorated white matter damage in the treated EAE mice. Correspondingly, the disease symptom score was greatly decreased, and motor ability was dramatically rescued in the iPSC-NSC-treated EAE mice, indicating the effectiveness of using iPSC-NSCs to treat MS. Our study provides pre-clinical evidence to support the feasibility of treating MS by transplantation of iPSC-derived NSCs.展开更多
Human endogenous retrovirus W env(HERV-W env) plays a critical role in many neuropsychological diseases such as schizophrenia and multiple sclerosis(MS). These diseases are accompanied by immunological reactions in th...Human endogenous retrovirus W env(HERV-W env) plays a critical role in many neuropsychological diseases such as schizophrenia and multiple sclerosis(MS). These diseases are accompanied by immunological reactions in the central nervous system(CNS). Microglia are important immunocytes in brain inflammation that can produce a gasotransmitter – nitric oxide(NO). NO not only plays a role in the function of neuronal cells but also participates in the pathogenesis of various neuropsychological diseases. In this study, we reported increased NO production in CHME-5 microglia cells after they were transfected with HERV-W env. Moreover, HERV-W env increased the expression and function of human inducible nitric oxide synthase(hi NOS) and enhanced the promoter activity of hi NOS. Microglial migration was also enhanced. These data revealed that HERV-W env might contribute to increase NO production and microglial migration ability in neuropsychological disorders by regulating the expression of inducible NOS. Results from this study might lead to the identification of novel targets for the treatment of neuropsychological diseases, including neuroinflammatory diseases, stroke, and neurodegenerative diseases.展开更多
基金supported by the National Natural Science Foundation of China(Grant 31700714)the Young Scholars Supporting Program of Nanjing University of Finance and Economics(Grant ZZZXW20001)the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘Neurodegenerative diseases(NDs)are a major threat to the elderly,and efficient therapy is rarely available.A group of phytochemicals has been shown to ameliorate NDs;however,poor stability,low bioavailability,and reduced drug accumulation in brain tissue limit their application in NDs.Therefore,a targeted drug delivery system is a feasible treatment strategy for NDs.Extracellular vesicles(EVs)possess many favorable bioactivities and are excellent carriers for targeting brain tissue.This review summarizes EVs as novel phytochemical carriers in ND therapy.First,we discuss the current challenges of ND therapy and the therapeutic effects of phytochemicals for NDs.Second,we highlight the ability of EVs to cross the blood-brain barrier and act as drug carriers to enhance the therapeutic efficacy of drugs for NDs.Finally,encapsulation strategies for phytochemicals in EVs are particularly reviewed,as they are critical for obtaining high loading efficacy and stable drug delivery systems.This review provides new insights into EV-based drug delivery systems for improving the therapeutic effect of phytochemicals for ND treatment.Therefore,the release rate and pharmacokinetics of phytochemicals should be well controlled to ensure the therapeutic efficacy of phytochemical-loaded EVs in the brain.
基金supported by the grants from the National Natural Science Foundation of China(No.30600197)the Specialized Research Fund for the Doctoral Program of Higher Education of China(No.20050285017)
文摘Polyglutamine （polyQ） diseases are a family of neurodegenerative disorders including Huntington’s disease, spinobulbar muscular atrophy,dentatorubral-pallidoluysian atrophy and several spinocerebellar ataxias.polyQ diseases are caused by abnormal expansion of CAG repeats in certain genes.The expanded CAG repeats are then translated into a series of abnormally expanded polyQ tracts.Such polyQ tracts may induce misfolding of the disease-causing proteins.The present review mainly focuses on the common characteristics of the pathogenesis of these polyQ diseases,including conformational transition of proteins and its influence on the function of these proteins,the correlation between decreased ability of proteoly-sis and late-onset polyQ diseases,and the relationship between wide expression of disease-causing proteins and selective neuronal death.
文摘Wnts comprise a large family of proteins that have shown to be part of a signaling cascade that regulates several aspects of develop- ment including organogenesis, mid brain development as welt as stem cell proliferation. Wnt signaling pathway plays different roles in the development of neuronal circuits and also in the adult brain, where it regulates synaptic transmission and plasticity. It has been also implicated in various diseases including cancer and neurodegenerative diseases, reflecting its relevance in fundamental biological pro- cesses. This review summarizes the progress about Wnts function in mature nervous system with a focus on Alzheimer＇s disease （AD）. We discuss the prospects of modulating canonical and non-canonical Wnt signaling as a strategy for neuroprotection. This will include the potential of Wnts to： （i） act as potent regulators of hippocampai synapses and impact in learning and memory; （ii） regulate adult neurogenesis; and finally （iii） control AD pathogenesis.
基金supported by the China National Basic Research Program(2013CB966901,2012CBA01303)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA01040108)+1 种基金National Thousand Young Talents Program to Tongbiao Zhaothe National Natural Science Foundation of China Program((31271592,31570995)to Tongbiao Zhao,(31400831)to Jiani Cao)
文摘Multiple sclerosis(MS) is an autoimmune disease of the central nervous system(CNS), with focal T lymphocytic infiltration and damage of myelin and axons. The underlying mechanism of pathogenesis remains unclear and there are currently no effective treatments. The development of neural stem cell(NSC) transplantation provides a promising strategy to treat neurodegenerative disease. However, the limited availability of NSCs prevents their application in neural disease therapy. In this study, we generated NSCs from induced pluripotent stem cells(iPSCs) and transplanted these cells into mice with experimental autoimmune encephalomyelitis(EAE), a model of MS. The results showed that transplantation of iPSC-derived NSCs dramatically reduced T cell infiltration and ameliorated white matter damage in the treated EAE mice. Correspondingly, the disease symptom score was greatly decreased, and motor ability was dramatically rescued in the iPSC-NSC-treated EAE mice, indicating the effectiveness of using iPSC-NSCs to treat MS. Our study provides pre-clinical evidence to support the feasibility of treating MS by transplantation of iPSC-derived NSCs.
基金supported by grants from the National Natural Sciences Foundation of China(No.31470264,No.81271820,No.30870789,and No.30300117)the Key Program of Natural Science Foundation of Hubei Province of China(No.2014CFA078)+1 种基金the Stanley Foundation from the Stanley Medical Research Institute(SMRI),USA(No.06R-1366),to Dr.Fan Zhuthe Scientific Innovation Team Project of Hubei Province of China(No.2015CFA009)
文摘Human endogenous retrovirus W env(HERV-W env) plays a critical role in many neuropsychological diseases such as schizophrenia and multiple sclerosis(MS). These diseases are accompanied by immunological reactions in the central nervous system(CNS). Microglia are important immunocytes in brain inflammation that can produce a gasotransmitter – nitric oxide(NO). NO not only plays a role in the function of neuronal cells but also participates in the pathogenesis of various neuropsychological diseases. In this study, we reported increased NO production in CHME-5 microglia cells after they were transfected with HERV-W env. Moreover, HERV-W env increased the expression and function of human inducible nitric oxide synthase(hi NOS) and enhanced the promoter activity of hi NOS. Microglial migration was also enhanced. These data revealed that HERV-W env might contribute to increase NO production and microglial migration ability in neuropsychological disorders by regulating the expression of inducible NOS. Results from this study might lead to the identification of novel targets for the treatment of neuropsychological diseases, including neuroinflammatory diseases, stroke, and neurodegenerative diseases.
