| Project/Area Number |
17590894
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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 |
Neurology
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| Research Institution | Keio University |
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Principal Investigator |
NIIKURA Takako Keio University, School of Medicine, Instructor (10301491)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Alzheimer's disease / Humanin / neuronal death / neuronrotective factor / peptide / peptide derivative / amyloid beta |
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| Research Abstract |
In Alzheimer's disease (AD), prevention of neuronal cell death should slow down the disease progression. Humanin (HN) is a 24-residue neuroprotective peptide (MAPRGFSCLLLLTSEIDLPVKRRA). In vitro studies showed that HN protected neurons from various types of AD-related insults, which include amyloid beta peptides and familial AD-linked mutants of amyloid precursor protein and presenilins. Amino acid replacement study revealed that the substitution of Ser14 to Gly (S14G-HN) drastically increased its action potency in vitro neuroprotection assays: S14G-HN is effective at 1-10nM of concentration whereas HN protects neurons at 1-10mM. Furthermore, S14G-HN ameliorated memory deficit induced by amylid beta by intracerebroventricular injection, while HN showed the same tendency that was not statistically significant. To elucidate action mechanism of HN and S14G-HN, we performed secondary structure analysis by circular dichroism. The secondary structure of these peptides was significantly different in phosphate-buffered saline. The structural change of S14G-HN was observed in a concentration and temperature-dependent manner, suggesting self-association via hydrophobic interaction.
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