Molecular Genetics of SCA1

描述（由申请人提供）：脊髓小脑性共济失调1型（SCA1）是九种致命的遗传性神经退行性疾病之一，由框架内CAG三核苷酸重复扩增引起。每个重复通道编码受影响蛋白中的一段谷氨酰胺残基，在SCA1的情况下，该蛋白是ataxin-1 （ATXN1）。SCA1的症状包括运动协调和平衡丧失、言语不清、吞咽困难、痉挛和一些认知障碍。SCA1病理的一个特征是小脑皮层的浦肯野细胞萎缩和最终丢失。与许多神经退行性疾病一样，SCA1是一种典型的晚发性疾病，表明衰老引起的生理变化有助于疾病的发病。目前尚无有效的治疗方法。因此，识别SCA1发病和进展的信号通路和细胞介质仍然是寻找治疗方法的主要挑战，也是本申请中概述的研究重点。

DESCRIPTION (provided by applicant): 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. Thus, identifying signaling pathways and cellular mediators of SCA1 onset and progression remain a major challenge in the search for therapeutics and is the focus of the research outlined in this application for continued support. )