靶向自噬途径作为亨廷顿舞蹈病的潜在治疗策略

Potential therapeutics targeting on autophagy for Huntington disease

亨廷顿舞蹈病的病理特征是神经元内存在突变亨廷顿蛋白聚集体,自噬是清除突变亨廷顿蛋白的重要途径之一。深入研究自噬形成分子调控机制对于治疗亨廷顿舞蹈病有重要意义。自噬可通过抑制哺乳动物西罗莫司(雷帕霉素)靶蛋白(mTOR)活性来调节,同时,自噬也受非mTOR依赖途径的调控。通过调节这两条途径可加速突变亨廷顿蛋白的清除,进而降低突变亨廷顿蛋白毒性作用。本文综述了5条能够调节自噬作用的途径的研究进展。

Huntington disease（HD） is characterized by the formation of intra-neuronal mutant huntingtin protein aggregates.Autophagy is an important clearance pathway for the removal of mutant huntingtin associated with HD.A keen insight into autophagy in terms of induction,formation and degradation,as revealed by accumulation studies,may formulate therapeutic strategies for HD.Autophagy is negatively regulated by the mammalian target of Rapamycin（mTOR） and can also be induced by mTOR-independent pathway.Both pathways enhance the clearance of mutant huntingtin fragments and attenuate polyglutamine toxicity.In this review,five pathways,inducing autophagy,which may be potential therapeutic targets for HD,are described.