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タイトル: BIN1 regulates BACE1 intracellular trafficking and amyloid-β production
著者: Miyagawa, Toji
Ebinuma, Ihori
Morohashi, Yuichi
Hori, Yukiko
Chang, Mee Young
Hattori, Haruhiko
Maehara, Tomoaki
Yokoshima, Satoshi
Fukuyama, Tohru
Tsuji, Shoji
Iwatsubo, Takeshi
Prendergast, George C.
Tomita, Taisuke
発行日: 2016年5月14日
出版者: Oxford University Press
掲載誌情報: Miyagawa T, Ebinuma I, Morohashi Y, Hori Y, Young Chang M, Hattori H, Maehara T, Yokoshima S, Fukuyama T, Tsuji S, Iwatsubo T, Prendergast GC, Tomita T, "BIN1 regulates BACE1 intracellular trafficking and amyloid-β production", Human Molecular Genetics Online Edition: 2016/05/14 (Japan time), doi:10.1093/hmg/ddw146.
関連URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/disruption-of-intracellular-transport-shown-to-trigger-alzheimers-disease.html
抄録: BIN1 is a genetic risk factor of late-onset Alzheimer disease (AD), which was identified in multiple genome-wide association studies. BIN1 is a member of the amphiphysin family of proteins, and contains N-terminal Bin-Amphiphysin-Rvs and C-terminal Src homology 3 domains. BIN1 is widely expressed in the mouse and human brains, and has been reported to function in the endocytosis and the endosomal sorting of membrane proteins. BACE1 is a type 1 transmembrane aspartyl protease expressed predominantly in neurons of the brain and responsible for the production of amyloid-β peptide (Aβ). Here we report that the depletion of BIN1 increases cellular BACE1 levels through impaired endosomal trafficking and reduces BACE1 lysosomal degradation, resulting in increased Aβ production. Our findings provide a mechanistic role of BIN1 in the pathogenesis of AD as a novel genetic regulator of BACE1 levels and Aβ production.
内容記述: UTokyo Research掲載「細胞内の輸送の乱れがアルツハイマー病を引き起こす」 URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/disruption-of-intracellular-transport-shown-to-trigger-alzheimers-disease.html
UTokyo Research "Disruption of intracellular transport shown to trigger Alzheimer’s disease" URI: http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/disruption-of-intracellular-transport-shown-to-trigger-alzheimers-disease.html
URI: http://hdl.handle.net/2261/72467
ISSN: 1460-2083
出現カテゴリ:014 自然科学
1207010 学術雑誌論文


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