Dopamin neuron specific modification of alpha-synulein and novel therapeutic target against Parkinson's disease
| Project/Area Number |
24591262
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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 |
Neurology
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| Research Institution | Tottori University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
MATSURA Tatusya 鳥取大学, 医学部, 教授 (00199746)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | パーキンソン病 / α-synuclein / ドパミン / カテコールアミン / メチオニン / α-シヌクレイン / 酸化修飾 / 翻訳後修飾 / ドーパミン |
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| Outline of Final Research Achievements |
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the selective loss of dopamine (DA) neurons. However, it is not well understood why PD-related pathogenesis occurs in DA neurons. We investigated the interaction between DA and a-synuclein (asyn) with regard to cytotoxicity. We generated PC12 cells expressing human asyn, as well as several asyn mutants using a Tet-OFF system. Overexpression of wildtype asyn decreased cell viability in long-term cultures, while an inhibitor of tyrosine hydroxylase blocked this vulnerability, suggesting that asyn-related cytotoxicity is associated with DA metabolism. The vulnerabilities of all mutant cell lines were lower than that of wildtype asyn-expressing cells. Moreover, asyn containing DA-mediated oxidized methionine (Met(O)) was detected in our cell lines. Met(O) was lower in methionine mutant cells, especially in the M127A mutant cells. Moreover, Y125 and S129 may act as enhancers of this DA-related modification of asyn.
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Depletion of p62 reduces nuclear inclusions and paradoxically ameliorates disease phenotypes in Huntington's model mice.2015
Author(s)
Kurosawa M, Matsumoto G, Kino Y, Okuno M, Kurosawa-Yamada M, Washizu C, Taniguchi H, Nakaso K, Yanagawa T, Warabi E, Shimogori T, Sakurai T, Hattori N, Nukina N.
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Journal Title
Hum Mol Genet
Volume: 24
Pages: 1092-1105
Related Report
Peer Reviewed
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[Journal Article] Deficiency of p62/Sequestosome 1 causes hyperphagia due to leptin resistance in the brain2013
Author(s)
Harada H, Warabi E, Matsuki T, Yanagawa T, Okada K, Uwayama J, Ikeda A, Nakaso K, Kirii K, Noguchi N, Bukawa H, Siow R, Mann G, Shoda J, Ishii T, and Sakurai T．
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Journal Title
J. Neurosci.
Volume: 33
Issue: 37
Pages: 14767-14777
DOI
Related Report
Peer Reviewed
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