Effects of PLK2 knockout on alpha-synuclein neurotoxicity
| Project/Area Number |
18K07386
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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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| Review Section |
Basic Section 51030:Pathophysiologic neuroscience-related
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| Research Institution | Yamagata University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | パーキンソン病 / αシヌクレイン / PLK2 / モデル動物 / アデノ随伴ウイルス / リン酸化 |
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| Outline of Final Research Achievements |
Aggregated alpha-synuclein (αS) accumulates in the Lewy bodies in Parkinson's disease. The effect of phosphorylation of Ser129, a major post-transcriptional modification, on neurotoxicity remains to be elucidated. In this we analyzed the effect of Ser129 phosphorylation by polo-like 2 (PLK2) on αS neurotoxicity. We injected recombinant adeno-associated virus (AAV)-A53TαS into the midbrain of PLK2 knockout mice and analyzed the dopamine neurotoxicity. The data suggested that dopamine neurotoxicity in PLK2 knockout mice might be suppressed than that in wild-type mice. Additional analysis is underway to determine if the neuroprotective effect is significant and the mechanism by which it is achieved.
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| Academic Significance and Societal Importance of the Research Achievements |
パーキンソン病は病理学的に黒質線条体のドパミン神経細胞の脱落とαシヌクレイン凝集体の形成によって特徴づけられる。リン酸化αSは主要な翻訳後修飾として知られるが、その病的意義は不明である。現在、αSによる神経毒性を緩和する治療薬は開発されていない。本研究によりSer129リン酸化のαS神経毒性への効果を明らかにすることにより、リン酸化レベルの調節が、神経保護効果を有する治療のターゲットとなりうるか明らかとなる可能性がある。
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Report
(5 results)
Research Products
(1 results)
