Molecular Genetics of SCA1

描述(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，由基础CAG三核苷酸重复序列扩张引起。每个重复序列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的症状包括失去运动协调和平衡，说话含糊不清，吞咽困难，痉挛，以及一些认知障碍。SCA1病理的一个特征是小脑皮质浦肯野细胞的萎缩和最终的丢失。像许多神经退行性疾病一样，SCA1通常是一种起病晚的疾病，这表明衰老引起的生理变化有助于疾病的发生。目前还没有有效的治疗方法。因此，识别SCA1发生和发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，以寻求持续的支持。)

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. )