| Project/Area Number |
09357005
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| Research Category |
Grant-in-Aid for Scientific Research (A).
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Neurology
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| Research Institution | KEIO university |
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Principal Investigator |
NISHIMOTO Ikuo KEIO university School of Medicine, Professor, 医学部, 教授 (80180652)
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| Co-Investigator(Kenkyū-buntansha) |
笹川 展幸 慶應義塾大学, 医学部, 専任講師 (20187107)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥25,800,000 (Direct Cost: ¥25,800,000)
Fiscal Year 1998: ¥10,800,000 (Direct Cost: ¥10,800,000)
Fiscal Year 1997: ¥15,000,000 (Direct Cost: ¥15,000,000)
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| Keywords | Alzhimer's disease / Neurodegenerative disease / Neuronal disease / APP / Go / βγサブユニット / 家族性アルツハイマー病 / 膜貫通型 |
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| Research Abstract |
Neuronal cell death is the central abnormality in Alzheimer's disease (AD). To establish curative therapy for AD, controlling neuronal cell death is therefore mandatory. An important clue in the development of AD therapy is to find the molecules that suppress neuronal cell death by familial Alzheimer's disease (FAD) genes and Aβ amyloid. Through disease-based death trap screening, we identified a novel gene, designated Humanin (HN) cDNA, which encodes a secretory 24 residue polypeptide. HN abolished death of neuronal cells by all known kinds of FAD genes-mutant APP, PS1 and PS2 and Aβ1-43 without effect on neuronal cell death by Huntington's disease/spinocerebellar ataxia-linked polyglutamine repeat Q79 or amyotrophic lateral sclerosis-causative SOD1 mutants. Therefore, HN is a selective and omnipotent suppressor of neuronal cell death caused by AD-relevant insults. The rescue action of HN was mediated by suppression of both Aβ-independent and -dependent neurotoxicities of FAD genes without any effect on Aβ production, suggesting that HN antagonizes against AD-relevant insults in a manner totally supplemental with Aβ-production inhibitors. The rescue action of HN was abolished by C8A, and potentiated by S14G, allowing S14G HN to be fully active at 1000 nM against all of the FAD genes and Aβ. This novel factor HN and its derivatives will contribute significantly to the development of curative therapy for AD.
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