Caspase和calpain在神经元凋亡和亨廷顿舞蹈病发病机制中的作用

The role of caspase and calpain in neuronal apoptosis and pathogenesis of Huntington disease

亨廷顿舞蹈病(Huntington disease,HD)是由亨廷顿蛋白(huntingtin,Htt)N端多聚谷氨酰胺序列延长引起的神经退行性疾病。一组半胱氨酸蛋白酶(caspase)和钙蛋白酶(calpain)可剪切突变Htt,产生毒性较大的N端Htt片段。近年的研究表明,该剪切作用导致N端片段的产生是舞蹈病发病机制中的重要一步,阻断这一过程可能为这种目前无法治愈的疾病提供潜在的治疗方案。

Huntington disease (HD) is a neurodegenerative disorder caused by an expansion of the polyglutamine tract in the N-terminal huntingtin (Htt). Htt is a substrate of caspases and calpains, the proteases involved in initiation and execution of neuronal apoptosis. Caspase- and calpain-mediated cleavage of mutant Htt results in the production of toxic N-terminal Htt fragments. Recent studies suggest that Htt cleavage may be a crucial step in the pathogenesis of HD and may be a potential molecular target for HD therapy.