Abstract：
Polyglutamine spinocerebellar ataxias (PolyQ SCAs) represent a group of monogenetic diseases in which the expanded polyglutamine repeats give rise to a mutated protein. The abnormally expanded polyglutamine protein produces aggregates and toxic species, causing neuronal dysfunction and neuronal death. The main symptoms of these disorders include progressive ataxia, motor dysfunction, oculomotor impairment, and swallowing problems. Nowadays, the current treatments are restricted to symptomatic alleviation, and no existing therapeutic strategies can reduce or stop the disease progression. Even though the origin of these disorders has been associated with polyglutamine-induced toxicity, RNA toxicity has recently gained relevance in polyQ SCAs molecular pathogenesis. Therefore, the research\'s focus on RNA metabolism has been increasing, especially on RNA-binding proteins (RBPs). The present review summarizes RNA metabolism, exposing the different processes and the main RBPs involved. We also explore the mechanisms by which RBPs are dysregulated in PolyQ SCAs. Finally, possible therapies targeting the RNA metabolism are presented as strategies to reverse neuropathological anomalies and mitigate physical symptoms.
摘要：
聚谷氨酰胺脊髓小脑共济失调（PolyQSCAs）代表一组单基因疾病，其中扩大的聚谷氨酰胺重复序列产生突变的蛋白质。异常膨胀的聚谷氨酰胺蛋白产生聚集体和有毒物质，导致神经元功能障碍和神经元死亡。这些疾病的主要症状包括进行性共济失调，运动功能障碍,动眼损伤,和吞咽问题。如今,目前的治疗仅限于对症缓解，并且没有现有的治疗策略可以减少或阻止疾病进展。尽管这些疾病的起源与聚谷氨酰胺诱导的毒性有关，RNA毒性最近在polyQSCAs分子发病机制中获得了相关性。因此,对RNA代谢的研究越来越关注，特别是在RNA结合蛋白（RBP）上。本综述概述了RNA代谢，暴露不同的过程和所涉及的主要RBP。我们还探索了PolyQSCA中RBP失调的机制。最后,针对RNA代谢的可能疗法被提出作为逆转神经病理异常和减轻身体症状的策略。
