Polyglutamine (polyQ) diseases are a group of hereditary neurodegenerative disorders caused by expansion of unstable polyQ repeats in their associated disease proteins. To date, the pathogenesis of each disease remains poorly understood, and there are no effective treatments. Growing evidence has indicated that, in addition to neurodegeneration, polyQ-expanded proteins can cause a wide array of abnormalities in peripheral tissues. Indeed, polyQ-expanded proteins are ubiquitously expressed throughout the body and can affect the function of both the central nervous system (CNS) and peripheral tissues. The peripheral effects of polyQ disease proteins include muscle wasting and reduced muscle strength in patients or animal models of spinal and bulbar muscular atrophy (SBMA), Huntington's disease (HD), dentatorubral-pallidoluysian atrophy (DRPLA), and spinocerebellar ataxia type 17 (SCA17). Since skeletal muscle pathology can reflect disease progression and is more accessible for treatment than neurodegeneration in the CNS, understanding how polyQ disease proteins affect skeletal muscle will help elucidate disease mechanisms and the development of new therapeutics. In this review, we focus on important findings in terms of skeletal muscle pathology in polyQ diseases and also discuss the potential mechanisms underlying the major peripheral effects of polyQ disease proteins, as well as their therapeutic implications.

中文翻译：

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聚谷氨酰胺疾病不断扩大的临床领域。

聚谷氨酰胺（polyQ）疾病是一组遗传性神经退行性疾病，由其相关疾病蛋白中不稳定的polyQ重复序列的扩增引起。迄今为止，每种疾病的发病机理仍然知之甚少，并且没有有效的治疗方法。越来越多的证据表明，除了神经退行性变以外，polyQ扩增的蛋白还可以引起周围组织的各种异常。实际上，polyQ扩增的蛋白质在人体中无处不在表达，并且会影响中枢神经系统（CNS）和周围组织的功能。polyQ疾病蛋白的外围作用包括在脊柱和延髓性肌肉萎缩症（SBMA），亨廷顿舞蹈病（HD），齿龈-上睑下垂肌萎缩症（DRPLA），和脊髓小脑共济失调17型（SCA17）。由于骨骼肌病理学可以反映疾病的进展，并且比中枢神经系统的神经退行性病变更易于治疗，因此了解polyQ疾病蛋白如何影响骨骼肌将有助于阐明疾病的机制和开发新的疗法。在这篇综述中，我们着重于polyQ疾病的骨骼肌病理学方面的重要发现，并讨论了polyQ疾病蛋白的主要外周效应的潜在机制及其治疗意义。了解polyQ疾病蛋白如何影响骨骼肌将有助于阐明疾病机制和开发新疗法。在这篇综述中，我们着重于polyQ疾病的骨骼肌病理学方面的重要发现，并讨论了polyQ疾病蛋白的主要外周效应的潜在机制及其治疗意义。了解polyQ疾病蛋白如何影响骨骼肌将有助于阐明疾病机制和开发新疗法。在这篇综述中，我们着重于polyQ疾病的骨骼肌病理学方面的重要发现，并讨论了polyQ疾病蛋白的主要外周效应的潜在机制及其治疗意义。