海藻糖治疗亨廷顿蛋白构象病的研究进展  

A novel therapeutic disaccharide for Huntington's disease by inhibiting aggregation and delaying pathology

作　　者：李昭华[1] 蒙健宗[2] 周礼圆[3] 董先智[1] 

机构地区：[1]中国科学院生物物理研究所蛋白质与多肽药物实验室,北京100101 [2]广西大学生命科学与技术学院,南宁530004 [3]广西壮族自治区人民医院,南宁530021

出　　处：《中国新药杂志》2009年第21期2032-2035,共4页Chinese Journal of New Drugs

摘　　要：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 autosomal dominant neurodegenerative disorder. It is caused by CAG trinucleotide repeat expansions that are translated into abnormally long polyglutamine tracts. One of the pathological hallmarks in HD is the formation of intranuclear inclusions of polyglutamine-containing proteins in the brain. Although causal relationships between polyglutamine aggregation and cellular toxicity are much debated, inhibition of the polyglutamine-mediated protein aggregation may provide treatment options for HD. The trehalose has a potential to inhibit polyglutamine-induced protein aggregation and to increase survival in a cellular model of HD. Oral administration of trehalose decreased polyglutamine aggregates in the cerebrum and liver, improved motor dysfunction and extended life span in a transgenic mouse model of HD.

关 键 词：亨廷顿病 海藻糖 多聚谷氨酰胺 分子伴侣 

分 类 号：R971[医药卫生—药品]