PDF(Pubmed)
Abstract：
Spinocerebellar ataxias (SCAs) are a rare autosomal dominant neurodegenerative disorder. To date, approximately 50 different subtypes of SCAs have been characterized. The prevalent types of SCAs are usually of PolyQ origin, wherein the disease pathology is a consequence of multiple glutamine residues being encoded onto the disease proteins, causing expansions. SCAs 2 and 3 are the most frequently diagnosed subtypes, wherein affected patients exhibit certain characteristic physiological manifestations, such as gait ataxia and dysarthria. Nevertheless, other clinical signs were exclusive to these subtypes. Recently, multiple molecular diagnostic methods have been developed to identify and characterize these subtypes. Despite these advancements, the molecular pathology of SCAs remains unknown. To further understand the mechanisms involved in neurodegenerative SCAs 2 and 3, patient-derived induced pluripotent stem cell (iPSC)-based modelling is a compelling avenue to pursue. We cover the present state of iPSC-based in-vitro illness modelling of SCA subtypes 2 and 3 below, along with a list of cell lines created, and the relevance of research outcomes to personalized autologous therapy.
摘要：
脊髓小脑共济失调（SCAs）是一种罕见的常染色体显性神经退行性疾病。迄今为止,已经表征了大约50种不同的SCA亚型。SCA的流行类型通常是PolyQ起源的，其中疾病病理是多个谷氨酰胺残基被编码到疾病蛋白上的结果，导致扩张。SCAs2和3是最常见的诊断亚型，其中受影响的患者表现出某些特征性的生理表现，如步态共济失调和构音障碍。然而，其他临床体征是这些亚型所独有的.最近,已经开发了多种分子诊断方法来鉴定和表征这些亚型。尽管取得了这些进步,SCAs的分子病理学仍然未知。为了进一步理解神经退行性SCAs2和3的机制，基于患者来源的诱导多能干细胞（iPSC）的建模是一个引人注目的途径。我们涵盖了以下基于iPSC的SCA亚型2和3的体外疾病建模的现状，连同创建的细胞系列表，以及研究结果与个性化自体治疗的相关性。
