Neuron-specific mechanism for production and secretion of amyloid-beta and therapeutic regulation of its deposition
Project/Area Number |
26430070
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Neurochemistry/Neuropharmacology
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Research Institution | Shiga University of Medical Science |
Principal Investigator |
NISHIMURA Masaki 滋賀医科大学, 神経難病研究センター, 教授 (40322739)
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Co-Investigator(Kenkyū-buntansha) |
J・P Bellier 滋賀医科大学, 神経難病研究センター, 助教 (80346022)
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | 認知症 / アルツハイマー病 / アミロイドβ / シナプス / Presenilin / ILEI / γセクレターゼ / 神経科学 / 神経変性疾患 |
Outline of Final Research Achievements |
The exact subcellular site and mechanism of Alzheimer disease-related Aβ secretion form neurons in vivo remain unresolved. (1) Using subcellular fractionation of mouse brain, we revealed that APP and components of the γ-secretase complex are localized to the active zone membrane and the active zone-docked synaptic vesicles of the presynaptic terminals. (2) We could not find any post-translational modification of synaptic Presenilin-1 which enhanced a relative ratio of Aβ42 production. (3) We found ILEI as a synaptic Aβ production-suppressing protein and tried molecular design for Aβ-reducing peptides or compounds by conformational prospect of the interaction between ILEI and Preseniin-1. We also found that this binding was dependent on the DQL sequence of Presenilin-1 C-terminal tail, and the 3 dimension-reference interaction site model (3D-RISM) theory predicted that candidate of Presenilin-1-binding region on ILEI is around a side chain of the Lys84 residue.
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Report
(4 results)
Research Products
(25 results)
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[Journal Article] Generation of transgenic cynomolgus monkeys that express green fluorescent protein throughout the whole body2016
Author(s)
Seita Y, Tsukiyama T, Iwatani C, Tsuchiya H, Matsushita J, Azami T, Okahara J, Nakamura S, Hayashi Y, Hitoshi S, Itoh Y, Imamura T, Nishimura M, Tooyama I, Miyoshi H, Saitou M, Ogasawara K, Sasaki E, Ema M
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Journal Title
Scientific Reports
Volume: 2
Issue: 1
Pages: 24868-24868
DOI
NAID
Related Report
Peer Reviewed / Open Access
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