title: Lipoprotein lipase deficiency leads to α-synuclein aggregation and ubiquitin C-terminal hydrolase L1 reduction.
abstract: We have previously reported that presynaptic dysfunction and cognitive decline have been found in lipoprotein lipase (LPL) deficient mice, but the mechanism remains to be elucidated. Accumulating evidence supported that α-synuclein (α-syn) and ubiquitin C-terminal hydrolase L1 (UCHL1) are required for normal synaptic and cognitive function. In this study, we found that α-syn aggregated and the expression of UCHL1 decreased in the brain of LPL deficient mice. Reduction of UCHL1 was resulted from nuclear retention of DNA cytosine-5-methyltransferase 1 in LPL knockout mice. Reverse changes were found in cultured cells overexpressing LPL. Furthermore, deficiency of LPL increased ubiquitination of α-syn. These results indicated that aggregation of α-syn and reduction of UCHL1 expression in LPL-deficient mice may affect synaptic function.
authors.affiliation: Neuroscience Research Institute, Peking University Health Science Center, Beijing 100191, China.
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.affiliation: Neuroscience Research Institute, Peking University Health Science Center, Beijing 100191, China.
authors.forename: T
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Neuroscience Research Institute, Peking University Health Science Center, Beijing 100191, China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Neuroscience Research Institute, Peking University Health Science Center, Beijing 100191, China.
authors.forename: T
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Neuroscience Research Institute, Peking University Health Science Center, Beijing 100191, China.
authors.forename: R
authors.initials: R
authors.lastname: Zhan
authors.affiliation: Neuroscience Research Institute, Peking University Health Science Center, Beijing 100191, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Neuroscience Research Institute, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Tong
authors.affiliation: Neuroscience Research Institute, Peking University Health Science Center, Beijing 100191, China.
authors.forename: X
authors.initials: X
authors.lastname: Tian
authors.affiliation: Neuroscience Research Institute, Peking University Health Science Center, Beijing 100191, China.
authors.forename: T
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Neuroscience Research Institute, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Diabetes and Obesity Research Center, Sanford/Burnham Medical Research Institute, La Jolla, CA 92037, USA.
authors.forename: X
authors.initials: X
authors.lastname: Han
authors.affiliation: Peking University Third Hospital, Beijing 100191, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.affiliation: Peking University Third Hospital, Beijing 100191, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Peking University Third Hospital, Beijing 100191, China.
authors.forename: X
authors.initials: X
authors.lastname: Guo
authors.affiliation: Peking University Third Hospital, Beijing 100191, China.
authors.forename: W
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Peking University Third Hospital, Beijing 100191, China.
authors.forename: D
authors.initials: D
authors.lastname: Fan
authors.affiliation: Institute of Cardiovascular Science, Health Science Center, Peking University, Beijing 100191, China.
authors.forename: G
authors.initials: G
authors.lastname: Liu
authors.affiliation: Neuroscience Research Institute, Peking University Health Science Center, Beijing 100191, China; Peking University Third Hospital, Beijing 100191, China. Electronic address: dchui@bjmu.edu.cn.
authors.forename: D
authors.initials: D
authors.lastname: Chui
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008072:Hyperlipoproteinemia Type I / Q000378:metabolism* / Q000473:pathology; D008071:Lipoprotein Lipase / Q000235:genetics; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013574:Synaptosomes / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*; D054875:Ubiquitination; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: C497604:SNCA protein, human; C497605:Snca protein, mouse; C482860:UCHL1 protein, human; D051844:alpha-Synuclein; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C000619381:Dnmt1 protein, mouse; D008071:Lipoprotein Lipase; D043222:Ubiquitin Thiolesterase; C496976:Uchl1 protein, mouse
keywords: DNA cytosine-5-methyltransferase 1; lipoprotein lipase; ubiquitin C-terminal hydrolase L1; α-synuclein