2007 Fiscal Year Final Research Report Summary
A role of spleen in the conformational transition of prion protein
| Project/Area Number |
16590857
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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 | Tokushima Bunri University (2005-2007)
Fukuoka University (2004) |
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Principal Investigator |
MATSUNAGA Yoichi Tokushima Bunri University, Pyarmacology, Professor (80239053)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Tatsuo Fukuoka University, Internal Medicine, Professor (60159217)
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| Project Period (FY) |
2004 – 2007
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| Keywords | prion / Amyloid-beta / neurotoxicity / dendritic cells / splenocytes / breaker peptides / stefin B / moltenglobule |
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| Research Abstract |
We explored the dynamics of 3 kinds of prion short peptides that is PrP101, 141 and 171-200 in mouse and clarified the preferential accumulation of protease K resistant PrP101-130 in spleen. The homology of sequences between A-beta42, Stefin B and PrP101-130 suggested that His at 111, Val at 120, Gly at 131 are the key amino acid residues to induce pathological aggregation in brain. Both of PrP and Amyloid-beta are molten-globule and we found that pH (4.6) and metal ions(Zn^<2+>, Cu^<2+>) affect the conformational transition in both Amyloid proteins. Based on the data, we explored the prion protein(PrP) breaker peptides in the mouse derived Neuronal cell(N2a). The PrP(101-130) is toxic to N2a cell and we tested 4 kinds of eight-residues peptides, namely breaker peptides PrP(101-109), PrP(103-112), PrP(115-124), PrP(128.137) to inhibit the PrP(101-130) toxicity. A potent inhibitory activity of se breaker peptides were assessed as the amount of remaining protein after PK digestion by Cell dot Western blot. In the present study, we could not find any breaker activity in these 4 peptides We also tested the same kinds of experiments to glia cells and also found no activity to inhibit the PK resistant formation. The other region of PrP peptides should be tested to inhibit the PrP(101-130) toxicity to the neuronal cells in the future study.
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