Angiotensin-(1–7)reducesα-synuclein aggregation by enhancing autophagic activity in Parkinson's disease  

作　　者：Qing Gao Rui Chen Liang Wu Qing Huang Xi-Xi Wang You-Yong Tian Ying-Dong Zhang 

机构地区：[1]Department of Neurology,Nanjing First Hospital,Nanjing Medical University,Nanjing,Jiangsu Province,China

出　　处：《Neural Regeneration Research》2022年第5期1138-1145,共8页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,No.81801263(to QG)。

摘　　要：Abnormal accumulation ofα-synuclein contributes to the formation of Lewy bodies in the substantia nigra,which is considered the typical pathological hallmark of Parkinson's disease.Recent research indicates that angiotensin-(1-7)plays a crucial role in several neurodegenerative disorders,including Parkinson's disease,but the underlying mechanisms remain elusive.In this study,we used intraperitoneal administration of rotenone to male Sprague-Dawley rats for 4 weeks to establish a Parkinson's disease model.We investigated whether angiotensin-(1-7)is neuroprotective in this model by continuous administration of angiotensin-(1-7)into the right substantia nigra for 4 weeks.We found that angiotensin-(1-7)infusion relieved characteristic parkinsonian behaviors and reducedα-synuclein aggregation in the substantia nigra.Primary dopaminergic neurons were extracted from newborn Sprague-Dawley rat substantia nigras and treated with rotenone,angiotensin-(1-7),and/or the Mas receptor blocker A-779 for 24 hours.After binding to the Mas receptor,angiotensin-(1-7)attenuated apoptosis andα-synuclein aggregation in rotenone-treated cells.Primary dopaminergic neurons were also treated with angiotensin-(1-7)and/or the autophagy inhibitor 3-methyladenine for 24 hours.Angiotensin-(1-7)increasedα-synuclein removal and increased the autophagy of rotenone-treated cells.We conclude that angiotensin-(1-7)reducesα-synuclein aggregation by alleviating autophagy dysfunction in Parkinson's disease.Therefore,the angiotensin-(1-7)/Mas receptor axis plays an important role in the pathogenesis of Parkinson's disease and angiotensin-(1-7)has potential therapeutic value for Parkinson's disease.All experiments were approved by the Biological Research Ethics Committee of Nanjing First Hospital(approval No.DWSY-2000932)in January 2020.

关 键 词：Α-SYNUCLEIN apoptosis AUTOPHAGY dopaminergic neuron Lewy bodies neurodegenerative diseases Parkinson's disease renin-angiotensin system ROTENONE substantia nigra 

分 类 号：R742.5[医药卫生—神经病学与精神病学]