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Targeting aggregation in the development of therapeutics for the treatment of Huntington's disease and other polyglutamine repeat diseases.

机译:在治疗亨廷顿氏病和其他聚谷氨酰胺重复病的治疗方法开发中靶向聚集。

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摘要

Huntington's disease (HD) is one of a number of familial polyglutamine (polyQ) repeat diseases. These neurodegenerative disorders are caused by expression of otherwise unrelated proteins that contain an expansion of a polyQ tract, rendering them toxic to specific subsets of vulnerable neurons. These expanded repeats have an inherent propensity to aggregate; insoluble neuronal nuclear and cytoplasmic polyQ aggregates or inclusions are hallmarks of the disorders [1,2]. In HD, inclusions in diseased brains often precede onset of symptoms, and have been proposed to be involved in pathogenicity [3-5]. Various strategies to block the process of aggregation have been developed in an effort to create drugs that decrease neurotoxicity. A discussion of the effect of antibodies, caspase inhibitors, chemical inhibitors, heat-shock proteins, suppressor peptides and transglutaminase inhibitors upon aggregation and disease is presented.
机译:亨廷顿舞蹈病(HD)是许多家族性聚谷氨酰胺(polyQ)重复性疾病之一。这些神经退行性疾病是由其他不相关的蛋白质表达引起的,这些蛋白质含有多聚Q道的扩增,从而使其对脆弱的神经元的特定子集有毒性。这些扩展的重复序列具有固有的聚集倾向。不溶性神经元核和细胞质polyQ聚集体或内含物是这些疾病的标志[1,2]。在高清中,患病大脑中的内含物通常在症状发作之前出现,并被认为与致病性有关[3-5]。为了产生降低神经毒性的药物,已经开发出各种阻止聚集过程的策略。讨论了抗体,胱天蛋白酶抑制剂,化学抑制剂,热激蛋白,抑制剂肽和转谷氨酰胺酶抑制剂对聚集和疾病的影响。

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