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Abstract：
Spinocerebellar ataxia type 7 (SCA7) is a progressive neurodegenerative disorder resulting from abnormal expansion of an uninterrupted polyglutamine (polyQ) repeat in its disease protein, ataxin-7 (ATXN7). ATXN7 is part of Spt-Ada-Gcn5 acetyltransferase (SAGA), an evolutionarily conserved transcriptional coactivation complex with critical roles in chromatin remodeling, cell signaling, neurodifferentiation, mitochondrial health and autophagy. SCA7 is dominantly inherited and characterized by genetic anticipation and high repeat-length instability. Patients with SCA7 experience progressive ataxia, atrophy, spasticity, and blindness. There is currently no cure for SCA7, and therapies are aimed at alleviating symptoms to increase quality of life. Here, we report novel Drosophila lines of SCA7 with polyQ repeats in wild-type and human disease patient range. We find that ATXN7 expression has age- and polyQ repeat length-dependent reduction in fruit fly survival and retinal instability, concomitant with increased ATXN7 protein aggregation. These new lines will provide important insight on disease progression that can be used in the future to identify therapeutic targets for SCA7 patients.
摘要：
脊髓小脑性共济失调7型（SCA7）是一种进行性神经退行性疾病，由其疾病蛋白中不间断的聚谷氨酰胺（polyQ）重复序列异常扩张引起，ataxin-7（ATXN7）。ATXN7是Spt-Ada-Gcn5乙酰转移酶（SAGA）的一部分，在染色质重塑中具有关键作用的进化保守的转录共激活复合物，细胞信号，神经分化，线粒体健康和自噬。SCA7主要是遗传的，其特征是遗传预期和高重复长度不稳定性。SCA7患者经历进行性共济失调，萎缩,痉挛,和失明。目前没有治愈SCA7的方法，治疗旨在缓解症状以提高生活质量。这里,我们报道了在野生型和人类疾病患者范围内具有polyQ重复的SCA7果蝇新品系。我们发现ATXN7表达在果蝇存活和视网膜不稳定中具有年龄和polyQ重复长度依赖性减少，伴随着ATXN7蛋白聚集的增加。这些新的产品线将为疾病进展提供重要的见解，将来可用于确定SCA7患者的治疗靶标。
