自噬在脑缺血中的双重作用及小分子治疗药物的研究进展  

The dual effects of autophagy in cerebral ischemia and small-molecular therapeutic drugs

作　　者：卜发倩 张吉发 帅雯 和龙 欧阳亮[1] BU FaQian;ZHANG JiFa;SHUAI Wen;HE Long;OUYANG Liang(State Key Laboratory of Biotherapy and Cancer Center,West China Hospital,and Collaborative Innovation Center of Biotherapy,Sichuan University,Chengdu 610041,China;BEIJING ZHONGGUANCUN ENTERPRISE ASSOCIATION OF BIOTECH.&PHARMA,Beijing 100101,China)

机构地区：[1]四川大学华西医院生物治疗国家重点实验室,成都610041 [2]北京市中关村生物工程和新医药企业协会,北京100101

出　　处：《中国科学：生命科学》2022年第12期1827-1843,共17页Scientia Sinica(Vitae)

基　　金：国家自然科学基金(批准号:81922064,81874290)资助。

摘　　要：自噬是一种溶酶体参与的细胞内降解过程,在维持细胞稳态和存活中发挥关键作用.越来越多研究表明,自噬在缺血性神经元损伤中承担重要角色,具有双重作用.多个小分子被发现可以通过调控自噬对脑缺血再灌注起到神经保护作用,有望成为缺血性中风的新治疗药物.本文主要阐述了自噬在脑缺血中的双重调控作用,为进一步探究脑缺血和自噬的关系提供了理论基础.此外,本文总结了近3年来研究发现的通过调控自噬治疗脑缺血的小分子化合物及其作用机制,讨论了其在中风治疗中的潜在应用.Autophagy is an intracellular degradation system through a lysosome-dependent pathway,which plays a critical role in maintaining cell homeostasis and survival.An increasing number of studies have shown that autophagy is important in the development of ischemia neuron injury with dual effects.Many compounds have been discovered to exhibit a neuroprotective effect through regulating autophagy in ischemia/reperfusion injury,and are expected to become potential drugs for the treatment of ischemic stroke.In this review,the modulation of autophagy in cerebral ischemia as well as its dual effects is discussed,which may provide ideas for further studies on the relationship between cerebral ischemia and autophagy.In addition,the compounds that have been discovered in recent three years to treat cerebral ischemia by regulating autophagy and their mechanisms of action are summarized,and their potential applications in stroke treatment are discussed.

关 键 词：自噬 脑缺血损伤 中风 自噬调节剂 

分 类 号：R743[医药卫生—神经病学与精神病学]