Polyglutamine/poly(Q) diseases are a group nine hereditary neurodegenerative disorders caused due to abnormally expanded stretches of CAG trinucleotide in functionally distinct genes. All human poly(Q) diseases are characterized by the formation of microscopically discernable poly(Q) positive aggregates, the inclusion bodies. These toxic inclusion bodies are responsible for the impairment of several cellular pathways such as autophagy, transcription, cell death, etc., that culminate in disease manifestation. Although, these diseases remain largely without treatment, extensive research has generated mounting evidences that various events of poly(Q) pathogenesis can be developed as potential drug targets. The present review article briefly discusses the key events of disease pathogenesis, model system-based investigations that support the development of effective therapeutic interventions against pathogenesis of human poly(Q) disorders, and a comprehensive list of pharmacological and bioactive compounds that have been experimentally shown to alleviate poly(Q)-mediated neurotoxicity. Interestingly, due to the common cause of pathogenesis, all poly(Q) diseases share etiology, thus, findings from one disease can be potentially extrapolated to other poly(Q) diseases as well.

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多聚谷氨酰胺疾病：发病机制和潜在的药物干预

聚谷氨酰胺/聚 (Q) 疾病是九组遗传性神经退行性疾病，由功能不同的基因中 CAG 三核苷酸异常扩展引起。所有人类 Poly(Q) 疾病的特征都是形成显微镜下可辨别的 Poly(Q) 阳性聚集体，即包涵体。这些有毒包涵体会损害多种细胞途径，例如自噬、转录、细胞死亡等，最终导致疾病表现。尽管这些疾病在很大程度上仍然没有得到治疗，但广泛的研究已经产生了越来越多的证据表明，poly(Q) 发病机制的各种事件可以开发为潜在的药物靶点。本综述文章简要讨论了疾病发病机制的关键事件、支持开发针对人类多聚（Q）疾病发病机制的有效治疗干预措施的基于模型系统的研究，以及已通过实验证明的药理和生物活性化合物的综合列表减轻聚（Q）介导的神经毒性。有趣的是，由于发病机制的共同原因，所有多聚（Q）疾病都有相同的病因，因此，一种疾病的发现也可以外推到其他多聚（Q）疾病。