Cell-based therapeutic strategies for treatment of spinocerebellar ataxias:an update  

作　　者：Joana Sofia Correia Sara Duarte-Silva António JoséSalgado Patrícia Maciel 

机构地区：[1]Life and Health Sciences Research Institute(ICVS),School of Medicine,University of Minho,Braga,Portugal [2]ICVS/3B’s–PT Government Associate Laboratory,Braga,Guimarães,Portugal

出　　处：《Neural Regeneration Research》2023年第6期1203-1212,共10页中国神经再生研究（英文版）

基　　金：funded by national funds;through the Foundation for Science and Technology (FCT)-project UIDB/50026/2020 and UIDP/50026/2020;by the National Ataxia Foundation (NAF)

摘　　要：Spinocerebellar ataxias are heritable neurodegenerative diseases caused by a cytosine-adenine-guanine expansion,which encodes a long glutamine tract(polyglutamine)in the respective wild-type protein causing misfolding and protein aggregation.Clinical features of polyglutamine spinocerebellar ataxias include neuronal aggregation,mitochondrial dysfunction,decreased proteasomal activity,and autophagy impairment.Mutant polyglutamine protein aggregates accumulate within neurons and cause neural dysfunction and death in specific regions of the central nervous system.Spinocerebellar ataxias are mostly characterized by progressive ataxia,speech and swallowing problems,loss of coordination and gait deficits.Over the past decade,efforts have been made to ameliorate disease symptoms in patients,yet no cure is available.Previous studies have been proposing the use of stem cells as promising tools for central nervous system tissue regeneration.So far,pre-clinical trials have shown improvement in various models of neurodegenerative diseases following stem cell transplantation,including animal models of spinocerebellar ataxia types 1,2,and 3.However,contrasting results can be found in the literature,depending on the animal model,cell type,and route of administration used.Nonetheless,clinical trials using cellular implants into degenerated brain regions have already been applied,with the expectation that these cells would be able to differentiate into the specific neuronal subtypes and re-populate these regions,reconstructing the affected neural network.Meanwhile,the question of how feasible it is to continue such treatments remains unanswered,with long-lasting effects being still unknown.To establish the value of these advanced therapeutic tools,it is important to predict the actions of the transplanted cells as well as to understand which cell type can induce the best outcomes for each disease.Further studies are needed to determine the best route of administration,without neglecting the possible risks of repetitive transplant

关 键 词：cell transplantation ENGRAFTMENT induced pluripotent stem cells mesenchymal stem cells neural progenitor cells NEUROPROTECTION polyglutamine spinocerebellar ataxias SECRETOME spinocerebellar ataxia stem cell therapy 

分 类 号：R741[医药卫生—神经病学与精神病学]