2023 Fiscal Year Final Research Report
Elucidation of the mechanism of abnormal activation of LRRK2 in the pathogenesis of Parkinson's disease and its pathological significance
Project/Area Number |
21K06558
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
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Research Institution | Teikyo University |
Principal Investigator |
Ito Genta 帝京大学, 薬学部, 講師 (10431892)
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Project Period (FY) |
2021-04-01 – 2024-03-31
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Keywords | パーキンソン病 / LRRK2 / Rab12 / Rab29 / リン酸化 / リソソーム |
Outline of Final Research Achievements |
The purpose of this study was to elucidate the mechanism by which abnormalities in the protein leucine-rich repeat kinase 2 (LRRK2), which causes Parkinson's disease (PD), a disease that causes motor dysfunction such as resting tremor in old age, is responsible for causing PD. LRRK2 has a function of adding phosphate to other proteins (phosphorylation), and we found that phosphorylation of Rab12 protein causes abnormal intracellular positioning of intracellular organelles called lysosomes, which are the intracellular waste degrading machinery. This finding may lead to the development of a new treatment for PD by clarifying the phenomena caused by the abnormal intracellular position of lysosomes.
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Free Research Field |
病態神経生化学
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Academic Significance and Societal Importance of the Research Achievements |
パーキンソン病は高齢者に多く発症する神経変性疾患であるが、その治療法は対症療法に限られており、発症メカニズムに基づいてパーキンソン病を根本的に治療する方法や、その進行を遅らせる方法は存在しない。パーキンソン病の発症には細胞内の老廃物を処理する装置であるリソソームの機能障害が関与することが以前から指摘されていた。本研究で見出したリソソームの細胞内における位置の変化がどのようにリソソームや細胞の機能に影響を与えるかは明らかでない。今後、これらを明らかにすることで、パーキンソン病の根本的治療法の開発につながると期待される。
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