| Project/Area Number |
16590840
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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 | Kyoto Prefectural University of Medicine |
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Principal Investigator |
MIZUNO Toshiki Kyoto Prefectural University of Medicine, medical department, Associate Professor, 医学研究科, 助教授 (30264782)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGUCHI Nozomi Kyoto Prefectural University of Medicine, medical department, Associate Professor, 医学研究科, 助教授 (40079752)
NAKAGAWA Masanori Kyoto Prefectural University of Medicine, medical department, Professor, 医学研究科, 教授 (50198040)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Neurosin / α-synuclein / serine protease / NAC domain / Neurosin / セリンプロテアーゼ / レビー小体 / アルツハイマー病 / パーキンソン病 / レビー小体型痴呆 / アルツハイマー |
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| Research Abstract |
Background : Neurosin (Kallikrein-6), one of the serine proteases predominantly expressed in the central nervous system, was reported to be possible to degrade α-synuclein, a key protein for Parkinson disease. However, cleavage site of α-synuclein by neurosin has not been detected. In this study, cleavage sites of α-synuclein were identified by LC/MS/MS.
Method : Degradations of wild and mutant α-synuclein by neurosin were evaluated semi-quantitatively by SDS-PAGE. Restricted fragments of α-synuclein cleaved by neurosin were examined by LC/MS/MS (Ion trap mass spectrometer ; LCQ Advatage, Themo Electron Corporation, Waltham, MA).
Results : The first cleaving site of α-synuclein was Lyn80, and secondly Lyn96, Lyn97, Asp115 and Asp121 were cleaved by neurosin. A30P mutant α-synuclein was degraded slower than wild α-synuclein by neurosin.
Interpretation : The dominant cleaving site of Lyn80 is the center of the NAC region, which is responsible for polymerization of the α-synuclein. Our results showed that neurosin can degrade α-synuclein and it may inhibit the polymerization of α-synuclein by cleaving the NAC region.
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