| Project/Area Number |
20591403
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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, 医学系研究科, 准教授 (10273632)
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| Co-Investigator(Kenkyū-buntansha) |
MORIHARA Takashi 大阪大学, 医学系研究科, 助教 (90403196)
TAKEDA Masatoshi 大阪大学, 医学系研究科, 教授 (00179649)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 小胞体ストレス / 分子シャペロン / 脳梗塞 / アルツハイマー病 / アポトーシス / 脳虚血 / 急性毒性 |
|---|
| Research Abstract |
The endoplasmic reticulum (ER) stress response is a defense system for dealing with the accumulation of unfolded proteins in the ER lumen. Recent reports have shown that ER stress is involved in the pathology of some neurodegenerative diseases and cerebral ischemia. In a screen for compounds that induce the ER-mediated chaperone BiP/GRP78 (BiP), we identified BiP inducer X (BIX). BIX preferentially induced BiP with slight inductions of GRP94, calreticulin, and CHOP. The induction of BiP mRNA by BIX was mediated by activation of ER stress response elements (ERSEs) upstream of the BiP gene, through the ATF6 pathway. Pretreatment of neuroblastoma cells with BIX reduced cell death induced by ER stress. Intracerebroventricular pretreatment with BIX reduced the area of infarction due to focal cerebral ischemia in mice. In the penumbra of BIX-treated mice, ER stress-induced apoptosis was suppressed, leading to a reduction in the number of apoptotic cells. Considering these results together, it appears that BIX induces BiP to prevent neuronal death by ER stress, suggesting that it may be a potential therapeutic agent for cerebral diseases caused by ER stress.
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