Abstract:
Polyglutamine (polyQ) diseases are a group of inherited neurodegenerative disorders caused by expanded cytosine-adenine-guanine (CAG) repeats encoding proteins with abnormally expanded polyglutamine tract. A total of nine polyQ disorders have been identified, including Huntington\'s disease, six spinocerebellar ataxias, dentatorubral pallidoluysian atrophy (DRPLA), and spinal and bulbar muscular atrophy (SBMA). The diseases of this class are each considered rare, yet polyQ diseases constitute the largest group of monogenic neurodegenerative disorders. While each subtype of polyQ diseases has its own causative gene, certain pathologic molecular attributes have been implicated in virtually all of the polyQ diseases, including protein aggregation, proteolytic cleavage, neuronal dysfunction, transcription dysregulation, autophagy impairment, and mitochondrial dysfunction. Although animal models of polyQ disease are available helping to understand their pathogenesis and access disease-modifying therapies, there is neither a cure nor prevention for these diseases, with only symptomatic treatments available. In this paper, we analyze data from the CAS Content Collection to summarize the research progress in the class of polyQ diseases. We examine the publication landscape in the area in effort to provide insights into current knowledge advances and developments. We review the most discussed concepts and assess the strategies to combat these diseases. Finally, we inspect clinical applications of products against polyQ diseases with their development pipelines. The objective of this review is to provide a broad overview of the evolving landscape of current knowledge regarding the class of polyQ diseases, to outline challenges, and evaluate growth opportunities to further efforts in combating the diseases.
摘要:
聚谷氨酰胺(polyQ)疾病是一组遗传性神经退行性疾病,由扩展的胞嘧啶-腺嘌呤-鸟嘌呤(CAG)重复编码具有异常扩展的聚谷氨酰胺束的蛋白质引起。总共发现了九种polyQ疾病,包括亨廷顿病,六个脊髓小脑共济失调,牙本质苍白萎缩(DRPLA),脊髓和延髓肌萎缩症(SBMA)。这一类的疾病都被认为是罕见的,然而,polyQ疾病构成了最大的单基因神经退行性疾病组。虽然polyQ疾病的每个亚型都有自己的致病基因,某些病理分子属性与几乎所有的polyQ疾病有关,包括蛋白质聚集,蛋白水解切割,神经元功能障碍,转录失调,自噬受损,和线粒体功能障碍。虽然polyQ疾病的动物模型可以帮助了解其发病机理和获得疾病改善疗法,这些疾病既没有治愈方法,也没有预防方法,只有对症治疗。在本文中,我们分析了CASContentCollection的数据,总结了多Q病的研究进展。我们研究了该地区的出版物景观,以提供对当前知识进步和发展的见解。我们回顾了讨论最多的概念,并评估了对抗这些疾病的策略。最后,我们通过其开发管道检查针对polyQ疾病的产品的临床应用。这篇评论的目的是提供有关polyQ疾病类别的当前知识的不断演变的景观的广泛概述,概述挑战,并评估增长机会,以进一步努力防治这些疾病。