Molecular genetics of neurodegenerative pathogenic and protective pathways: The SCA1 perspective

项目摘要 脊髓小脑性共济失调1型(SCA1)是9种致死性遗传性神经退行性疾病之一 由基础CAG三核苷酸重复序列扩大引起的疾病。每个重复区段 在受影响的蛋白质中编码一段谷氨酰胺残基，在SCA1的情况下 蛋白质是ataxin-1(ATXN1)。SCA1的症状包括运动协调能力丧失和 平衡，说话含糊，吞咽困难，痉挛，以及一些认知障碍。 SCA1病理的一个特征是浦肯野细胞的萎缩和最终的丧失 来自小脑皮质。像许多神经退行性疾病一样，SCA1通常是一种 晚发性疾病表明，由于衰老引起的生理变化有助于 疾病的发病。目前还没有有效的治疗方法。识别信令 小脑中SCA1致病的途径和细胞介质导致 共济失调和作为致命性基础的脑干中的共济失调在寻找 治疗学，是本申请中概述的研究重点 支持。

Project Summary Spinocerebellar ataxia type 1 (SCA1) is one of nine fatal inherited neurodegenerative diseases caused by expansion of an inframe CAG trinucleotide repeat. Each repeat tract encodes a stretch of glutamine residues in the affected protein, in the case of SCA1 the protein is ataxin-1 (ATXN1). Symptoms of SCA1 include loss of motor coordination and balance, slurred speech, swallowing difficulty, spasticity, and some cognitive impairment. A characteristic feature of SCA1 pathology is atrophy and eventual loss of Purkinje cells from the cerebellar cortex. Like many neurodegenerative disorders, SCA1 is typically a late onset disease suggesting that physiological changes due to aging contribute to the onset of the disease. There is currently no effective treatment. Identifying signaling pathways and cellular mediators of SCA1 pathogenesis in the cerebellum leading to ataxia and in the brainstem that underlie lethality are critical in the search for therapeutics and are the focus of the research outlined in this application for continued support.