Clk1 deficiency promotes neuroinflammation and subsequent dopaminergic cell death through regulation of microglial metabolic reprogramming

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• 作者：Ruinan Gu^a ; Fali Zhang^a ; Gang Chen^b ; Chaojun Han^a ; Jay Liu^b ; Zhaoxiang Ren^a ; Yi Zhu^a ; John L. Waddington^a ; ^c ; Long Tai Zheng^a ; ^{zhenglongtai@suda.edu.cn} ; Xuechu Zhen^a ; ^{xuechuzhen@suda.edu.cn}
• 关键词：Clk1 ; Microglia ; Glycolysis ; MPTP ; mTOR/HIF-1α
• 刊名：Brain, Behavior, and Immunity
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：60
• 期：Complete
• 页码：206-219
• 全文大小：4518 K
• 卷排序：60

文摘

Clk1/COQ7 is a mitochondrial hydroxylase that is necessary for the biosynthesis of ubiquinone. Reduced expression of Clk1 in microglia enhanced inflammatory responses and aerobic glycolysis. Inhibition of glycolysis abolished Clk1 deficiency-induced hypersensitivity to inflammation. mTOR/HIF-1α and ROS/HIF-1α pathways are involved in Clk1 deficiency-induced aerobic glycolysis. Clk1+/− mice showed more severe DA neuron loss in MPTP induced mouse model of Parkinson’s disease.