Polyglutamine spinocerebellar ataxias (polyQ SCAs) include SCA1, SCA2, SCA3, SCA6, SCA7, and SCA17 and constitute a group of adult onset neurodegenerative disorders caused by the expansion of a CAG repeat sequence located within the coding region of specific genes, which translates into polyglutamine tract in the corresponding proteins. PolyQ SCAs are characterized by degeneration of the cerebellum and its associated structures and lead to progressive ataxia and other diverse symptoms. In recent years, gene and epigenetic deregulations have been shown to play a critical role in the pathogenesis of polyQ SCAs. Here, we provide an overview of the functions of wild type and pathogenic polyQ SCA proteins in gene regulation, describe the extent and nature of gene expression changes and their pathological consequences in diseases, and discuss potential avenues to further investigate converging and distinct disease pathways and to develop therapeutic strategies.

中文翻译：

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多聚谷氨酰胺扩增脊髓小脑性共济失调的基因失调和潜在机制

聚谷氨酰胺脊髓小脑性共济失调 (polyQ SCA) 包括 SCA1、SCA2、SCA3、SCA6、SCA7 和 SCA17，由位于特定基因编码区内的 CAG 重复序列扩增引起的一组成人发病神经退行性疾病，其转化为相应蛋白质中的聚谷氨酰胺束。PolyQ SCA 的特征是小脑及其相关结构的退化，并导致进行性共济失调和其他各种症状。近年来，基因和表观遗传失调已被证明在 polyQ SCA 的发病机制中起着关键作用。在这里，我们概述了野生型和致病性 polyQ SCA 蛋白在基因调控中的功能，描述了基因表达变化的程度和性质及其在疾病中的病理后果，