2014 Fiscal Year Final Research Report
Drug discovery research for Alzheimer's disease focused on molecular chaperone
| Project/Area Number |
24590084
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Keio University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | βアミロイド / アルツハイマー / 分子シャペロン / Heat shock protein |
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| Outline of Final Research Achievements |
We here examined the effect of geranylgeranylacetone, an inducer of heat shock protein (HSP) 70 expression, on the Alzheimer’s disease (AD)-related phenotypes. Repeated oral administration of geranylgeranylacetone to APP23 mice for 9 months not only improved cognitive function but also decreased levels of amyloid-β peptide (Aβ), Aβ plaque deposition and synaptic loss. These outcomes were similar to those observed in APP23 mice genetically modified to overexpress HSP70. Although the repeated oral administration of geranylgeranylacetone did not increase the level of HSP70 in the brain, a single oral administration of geranylgeranylacetone significantly increased the level of HSP70 when Aβ was concomitantly injected directly into the hippocampus. Since geranylgeranylacetone has already been approved for use as an anti-ulcer drug and its safety in humans has been confirmed, we propose that this drug be considered as a candidate drug for the prevention of AD.
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| Free Research Field |
薬理学
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