Activated Cyclin-Dependent Kinase 5 Promotes Microglial Phagocytosis of   Fibrillar beta-Amyloid by Up-regulating Lipoprotein Lipase Expression

doi:10.1074/mcp.M112.026864

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	Activated Cyclin-Dependent Kinase 5 Promotes Microglial Phagocytosis of Fibrillar beta-Amyloid by Up-regulating Lipoprotein Lipase Expression
	Ma, Yuanhui ; Bao, Jintao ; Zhao, Xuyang ; Shen, Hongyan ; Lv, Junniao ; Ma, Shuaipeng ; Zhang, Xuefei ; Li, Zeyang ; Wang, Shuxin ; Wang, Qingsong ; Ji, Jianguo
刊名	molecular cellular proteomics
	2013
关键词	HEPARAN-SULFATE PROTEOGLYCANS LOW-DENSITY-LIPOPROTEIN ALZHEIMERS-DISEASE APOLIPOPROTEIN-E A-BETA ENRICHMENT ANALYSIS SCAVENGER RECEPTOR MURINE MICROGLIA CELL-CULTURE AMINO-ACIDS
DOI	10.1074/mcp.M112.026864
英文摘要	Amyloid plaques are crucial for the pathogenesis of Alzheimer disease (AD). Phagocytosis of fibrillar beta-amyloid (A beta) by activated microglia is essential for A beta clearance in Alzheimer disease. However, the mechanism underlying A beta clearance in the microglia remains unclear. In this study, we performed stable isotope labeling of amino acids in cultured cells for quantitative proteomics analysis to determine the changes in protein expression in BV2 microglia treated with or without A beta. Among 2742 proteins identified, six were significantly up-regulated and seven were down-regulated by A beta treatment. Bioinformatic analysis revealed strong over-representation of membrane proteins, including lipoprotein lipase (LPL), among proteins regulated by the A beta stimulus. We verified that LPL expression increased at both mRNA and protein levels in response to A beta treatment in BV2 microglia and primary microglial cells. Silencing of LPL reduced microglial phagocytosis of A beta, but did not affect degradation of internalized A beta. Importantly, we found that enhanced cyclin- dependent kinase 5 (CDK5) activity by increasing p35-to-p25 conversion contributed to LPL up-regulation and promoted A beta phagocytosis in microglia, whereas inhibition of CDK5 reduced LPL expression and A beta internalization. Furthermore, A beta plaques was increased with reducing p25 and LPL level in APP/PS1 mouse brains, suggesting that CDK5/p25 signaling plays a crucial role in microglial phagocytosis of A beta. In summary, our findings reveal a potential role of the CDK5/p25-LPL signaling pathway in A beta phagocytosis by microglia and provide a new insight into the molecular pathogenesis of Alzheimer disease.; Biochemical Research Methods; SCI(E); PubMed; 4; ARTICLE; 10; 2833-2844; 12
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/319930]
专题	生命科学学院
推荐引用方式 GB/T 7714	Ma, Yuanhui,Bao, Jintao,Zhao, Xuyang,et al. Activated Cyclin-Dependent Kinase 5 Promotes Microglial Phagocytosis of Fibrillar beta-Amyloid by Up-regulating Lipoprotein Lipase Expression[J]. molecular cellular proteomics,2013.
APA	Ma, Yuanhui.,Bao, Jintao.,Zhao, Xuyang.,Shen, Hongyan.,Lv, Junniao.,...&Ji, Jianguo.(2013).Activated Cyclin-Dependent Kinase 5 Promotes Microglial Phagocytosis of Fibrillar beta-Amyloid by Up-regulating Lipoprotein Lipase Expression.molecular cellular proteomics.
MLA	Ma, Yuanhui,et al."Activated Cyclin-Dependent Kinase 5 Promotes Microglial Phagocytosis of Fibrillar beta-Amyloid by Up-regulating Lipoprotein Lipase Expression".molecular cellular proteomics (2013).