Loss of microglial autophagy causes Parkinson disease-like symptom in mice  

作　　者：CHENG Jin-bo LIAO Ya-jin LI Xiao-heng DONG Yuan TANG Bai-sha 袁增强 

机构地区：[1]Institute of Basic Medical Sciences,AMMS [2]Capital Medical University [3]Qingdao University,College of Medicine [4]Xiangya Hospital,Zhongnan University [5]中国神经科学学会 [6]中国卒中学会 [7]北京市生化学会 [8]北京市神经科学学会

出　　处：《中国药理学与毒理学杂志》2017年第5期462-462,共1页Chinese Journal of Pharmacology and Toxicology

摘　　要：Microglia activation induced neuroinflammation closely relates with the development of Parkinson disease. Autophagy regulates many biological processes,but the role in microglial activation and the development of Parkinson disease is not clear. In this study,we show that loss of microglial Atg5 cause neuroinflammation and motor and cognitive learning impairment in mice,with accumulation of α-synuclein and decrease of dopamine levels in the striatum. Inhibition of autophagy aggravates the activation of NLRP3 inflammasome via PDE10a-cAMP signaling in microglia. Furthermore,the downstream cytokine IL-1 increases Mif levels in a transcriptional dependent manner. Interestingly,Mif levels are significantly elevated in Parkinson disease patients. Taken together,our results reveal a protective role of autophagy in microglial activation-driven Parkinson disease,thus providing a potential targets for the clinical treatment.Microglia activation induced neuroinflammation closely relates with the development of Parkinson disease. Autophagy regulates many biological processes,but the role in microglial activation and the development of Parkinson disease is not clear. In this study,we show that loss of microglial Atg5 cause neuroinflammation and motor and cognitive learning impairment in mice,with accumulation of α-synuclein and decrease of dopamine levels in the striatum. Inhibition of autophagy aggravates the activation of NLRP3 inflammasome via PDE10a-cAMP signaling in microglia. Furthermore,the downstream cytokine IL-1 increases Mif levels in a transcriptional dependent manner. Interestingly,Mif levels are significantly elevated in Parkinson disease patients. Taken together,our results reveal a protective role of autophagy in microglial activation-driven Parkinson disease,thus providing a potential targets for the clinical treatment.

关 键 词：MICROGLIA Parkinson disease AUTOPHAGY 

分 类 号：R742.5[医药卫生—神经病学与精神病学]