2004 Fiscal Year Final Research Report Summary
Molecular mechanism of endoplasmic reticulum stress and Alzheimer disease
| Project/Area Number |
15591221
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Osaka University |
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Principal Investigator |
KUDO Takashi Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (10273632)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEDA Masatoshi Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (00179649)
TANAKA Toshihisa Osaka University, Graduate School of Medicine, Lecture, 医学系研究科, 講師 (10294068)
KAMINO Kohjin Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (40307955)
OHKOCHI Masayasu Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (90335357)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Alzheimer disease / β-amyloid / endoplasmic reticulum stress / molecular chaperone |
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| Research Abstract |
Our previous reports showed that endoplasmic reticulum (ER) stress response was down-regulated in presenilin-1 mutant cells. Following the amyloid cascade hypothesis, we developed an interest in investigating the effects of ER stress on amyloid-β peptide (Aβ) generation. In the present study, we showed that treatment with an ER stressor resulted in the reduction of Aβ 40 and Aβ 42 generation. Immunocytochemical study and immunoblotting of subfractions showed that ER stress caused dislocation of amyloid precursor protein (APP) from late compartments to early compartments during the secretory pathway, and decreased levels of released Aβ by β and γ cutting despite no reduction of its secretase activities. Co-immunoprecipitation study showed that ER stress response facilitated binding of BiP/GRP78 to APP to be retained in early compartments, such as ER. In dominant-negative cells for ER stress, the reduction system of Aβ may deteriorate to cause relative accumulation of Aβ. These findings suggest that induction of BiP/GRP78 by ER stress may be one regulatory mechanism for Aβ generation.
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Research Products
(7 results)
