| 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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| 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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