Analysis of sequential endoproteolytic process of beta-APP to establish novel therapeutic interventions
Project/Area Number |
17390318
|
Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Psychiatric science
|
Research Institution | Osaka University |
Principal Investigator |
TAKEDA Masatoshi Osaka University, Graduate School of Medicine, Professor (00179649)
|
Co-Investigator(Kenkyū-buntansha) |
OKOCHI Masayasu Osaka University, Graduate School of Medicine, Assistant (90335357)
KUDO Takashi Osaka University, Graduate School of Medicine, Associate Professor (10273632)
TANAKA Toshihisa Osaka University, graduate School of Medicine, Lecturer (10294068)
TAGAMI Shinji Osaka University, Graduate School of Medicine, Assistant (40362735)
MORIHARA Takashi Osaka University, Graduate School of Medicine, Assistant (90403196)
紙野 晃人 大阪大学, 医学系研究科, 助手 (40307955)
|
Project Period (FY) |
2005 – 2006
|
Project Status |
Completed (Fiscal Year 2006)
|
Budget Amount *help |
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2006: ¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 2005: ¥8,300,000 (Direct Cost: ¥8,300,000)
|
Keywords | Alzheimer disease / Presenilin / gamma-secretase / Notch signaling / Amyloid-beta peptide / beta-amyloid protein precursor / Notch-1 / gamma-cleavage |
Research Abstract |
We have revealed detailed processes of sequential endoproteolysis of betaAPP and Notch. We have found that novel compound-W is a second generation gamma-secretase inhibitor which inhibits Abeta generation without perturbing Notch signaling. Moreover, we found that Abeta29-40 peptide has an activity to inhibit beta-secretase. Furthermore, we established ELISA system to measure Nbeta level in vivo. In addition, we accidentally found compound-OSX which inhibit beta-cleavage of betaAPP without inhibiting BACE.
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Report
(3 results)
Research Products
(69 results)
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[Journal Article] Presenilin-dependent γ-secretase on plasma membrane and endosomes is functionally distinct2006
Author(s)
Fukumori A, Okochi M, Tagami S, Jiang J, Itoh N, Nakayama T, Yanagida K, Ishizuka-Katsura Y, Morihara T, Kamino K, Tanaka T, Kudo T, Tanii H, Ikuta A, Haass C, Takeda M.
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[Journal Article] Presenilin-dependent gamma-secretase on plasma membrane and endosomes is functionally distinct.2006
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[Journal Article] Toll-like receptor 3 mediated hyperphosphorylation of tauin human SH-SY5Y neuroblastoma cells.2006
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[Journal Article] S46-51 Tanii H, Tanaka T, Oku N, Takeda M. Neural substrates of emotionally valenced episodic memory : A PET study using film stimuli.2006
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