| Project/Area Number |
11670641
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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 | JUNTENDO UNIVERSITY |
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Principal Investigator |
HATTORI Nobutaka Juntendo University, School of Mad. , Lecturer, 医学部, 講師 (80218510)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMINE Hiroto Juntendo Univ. , School of Med. , Assistant Prof., 医学部, 助手 (90255670)
KOBAYASHI Tomonori Juntendo Univ. , School of Med. , Assistant. Prof., 医学部, 助手 (50266053)
MIZUNO Yoshikuni Juntendo Univ. , School of Med. , Professor, 医学部, 教授 (30049043)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | AR-JP / Ubiquitin-protein ligase / Young onset Parkinson7s disease / Lewy body / UbcH7 / Ubiquitin-proteasome pathway / 家族性パーキンソン病 / ユビキチン / RING finger motif |
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| Research Abstract |
The contribution of genetic factors to the pathogenesis of Parkinson's disease (PD) is supported by the existence of familial PD by single gene defect. Recently, several genes for inherited forms of PD have been mapped and/or identified. α-Synuclein is involved in a rare form of autosomal dominant form of familial PD with doparesponsive parkinsonism features and Lewy body-positive pathology. In contrast, the gene for an autosomal recessive juvenile parkinsonism (AR-JP) was found to be caused by mutations of the pakin gene. AR-JP is the most popular form of early-onset PD.The gene encoded a protein with a partial homology to ubiquitin in the N terminal portion and two RNG-finger like motives with IBR (in-between RINGs). To date, a variety of mutations including exon rearrangements and point mutations have been identified. In addition, pal-kin is localized on the Golgi complex, indicating that parkin may be involved in the axonal transport system. More recently, we have found that parkin interacts with the ubiquitin-conjugating enzyme E2 and is functionally linked to the Ub-proteasome pathway as a ubiquitin-protein ligase, E3. Theses characteristics of a lack of Lewy bodies which are considered to be a pathological hallmark. Our findings should enhance the exploration of the mechanisms of neuronal death as well as other neurodegenerative disorders of which variable inclusion bodies are observed.
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