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 Park...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.展开更多
文摘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.
