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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| 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 |
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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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Report
(4 results)
Research Products
(34 results)
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[Journal Article] Regulation of ER molecular chaperone prevents bone loss in a murine model for osteoporosis2010
Author(s)
Hino S-I, Kondo S, Yoshinaga K, Saito A, Murakami T, Kanemoto S, Sekiya H, Chihara K, Aikawa Y, Hara H, Kudo T, Sekimoto T, Funamoto T, Chosa E, Imaizumi K
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Journal Title
J Bone Miner Metab
Volume: 28
Pages: 131-138
NAID
Related Report
Peer Reviewed
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[Journal Article] The production ratios of AICDε51 and Aβ42 by intramembrane proteolysis of βAPP do not always change in parallel2010
Author(s)
Kohji Mori, Masayasu Okochi, Shinji Tagami, Taisuke Nakayama, Kanta Yanagida, Takashi S.Kodama, Shin-ichi Tatsumi, Kana Fujii, Hitoshi Tanimukai, Ryota Hashimoto, Takashi Morihara, Toshihisa Tanaka, Takashi Kudo, Satoru Funamoto, Yasuo Ihara, Masatoshi Takeda
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Journal Title
Psychogeriatrics
Volume: 10
Pages: 117-123
NAID
Related Report
Peer Reviewed
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[Journal Article] The impact of a genome-wide supported psychosis variant in the ZNF804A gene on memory function in schizophrenia2010
Author(s)
Hashimoto R, Ohi K, Yasuda Y, Fukumoto M, Iwase M, Iike N, Azechi M, Ikezawa K, Takaya M, Takahashi H, Yamamori H, Okochi T, Tanimukai H, Tagami S, Morihara T, Okochi M, Tanaka T, Kudo T, Kazui H, Iwata N, Takeda M
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Journal Title
Am J Med Genet B Neuropsychiatr Genet
Volume: 153B(8)
Pages: 1459-64
Related Report
Peer Reviewed
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[Journal Article] KIBRA Genetic Polymorphism Influences Episodic Memory in Alzheimer's Disease, but Does Not Show Association with Disease in a Japanese Cohort.2010
Author(s)
Hayashi N, Kazui H, Kamino K, Tokunaga H, Takaya M, Yokokoji M, Kimura R, Kito Y, Wada T, Nomura K, Sugiyama H, Yamamoto D, Yoshida T, Currais A, Soriano S, Hamasaki T, Yamamoto M, Yasuda Y, Hashimoto R, Tanimukai H, Tagami S, Okochi M, Tanaka T, Kudo T, Morihara T, Takeda
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Journal Title
Dement Geriatr Cogn Disord
Volume: 25;30(4)
Pages: 302-308
Related Report
Peer Reviewed
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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
Related Report
Peer Reviewed
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