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亨廷顿病(Huntington’s disease,HD)是一种由于蛋白质多聚谷氨酰胺序列伸展延长导致该蛋白质反常折叠凝集而引起的神经退行性疾病。含延长多聚谷氨酰胺序列的蛋白质聚集在中枢神经系统的神经元中形成包涵体(inclusions)和聚集体(aggregates),对神经细胞产生毒性。抑制多聚谷氨酰胺的蛋白质聚集成为治疗HD的研究策略之一。海藻糖是一种小分子糖类化合物,研究表明它能够抑制体外含多聚谷氨酰胺蛋白质的聚集,并具有提高亨廷顿病细胞模型存活率和改善亨廷顿小鼠病理的生理功能。文中就海藻糖稳定突变的亨廷顿蛋白的构象变化、抑制亨廷顿蛋白聚集体的形成、减缓HD症状的研究进行综述。
Huntington’s disease (HD) is a neurodegenerative disease caused by the unfolding and agglutination of the protein due to prolonged extension of the protein polyglutamine sequence. Proteins that contain prolonged polyglutamine sequences accumulate inclusions and aggregates in the neurons of the central nervous system, creating toxicity to nerve cells. Inhibition of polyglutamine protein aggregation has become one of the research strategies for the treatment of HD. Trehalose, a small molecule carbohydrate, has been shown to inhibit the aggregation of polyglutamine-containing proteins in vitro and to increase the survival of Huntington’s disease cell models and to improve the physiology of Huntington’s disease. In this paper, we reviewed the conformational changes of Huntington’s protein with stable mutant trehalose, the inhibition of the formation of Huntington’s protein aggregates and the alleviation of HD symptoms.