2010 Fiscal Year Final Research Report
Application of an ER chaperone inducer for Alzheimer disease
| 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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| 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 |
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| 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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[Journal Article] Effect of an Inducer of BiP, a Molecular Chaperone, on Endoplasmic Reticulum (ER) Stress-Induced Retinal Cell Death.2009
Author(s)
Inokuchi Y., Nakajima Y., Shimazawa M., Kurita T., Kubo M., Saito A., Sajiki H., Kudo T., Aihara M., Imaizumi K., Araie M., Hara H.
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Journal Title
Invest. Ophthalmol. Vis. Sci 50
Pages: 334-344
Peer Reviewed
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