Detoxification of aldehyde-conjugation as a new mechanism for preventing onset of Parkinson's disease
| Project/Area Number |
18H02443
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 44010:Cell biology-related
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
MATSUDA Noriyuki 公益財団法人東京都医学総合研究所, 基礎医科学研究分野, プロジェクトリーダー (10332272)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2019: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2018: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Keywords | DJ-1 / オキソアルデヒド / ヒドロキシ酸 / 解毒 / 加水酵素 / ミトコンドリア / アルデヒド / パーキンソン病 / グリオキサール / メチルグリオキサール / Thermal shift assay / 加水分解酵素 |
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| Outline of Final Research Achievements |
We have shown that DJ-1, a causative gene product of hereditary recessive Parkinson's disease, has enzymatic activity to hydrolyze α-oxaldehyde (such as glyoxal and methylglyoxal) to α-hydroxy acids. The activity of DJ-1 as α-oxoaldehyde hydratase can be clearly observed in vitro. Moreover, this activity was used as an indicator to identify DJ-1 inhibitors by overseas research groups (e.g., Eur. J. Pharmacol. 2022, Pubmed ID: 35605658), indicating that this enzymatic-activity of DJ-1 is reproducible.
Furthermore, during this research, we found an unexpected link between the "glyoxylate-binding activity of DJ-1 reflecting the α-oxaldehyde hydratase activity" and the "mitochondrial localization of DJ-1 harboring pathogenic mutations".
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| Academic Significance and Societal Importance of the Research Achievements |
多数の論文から、遺伝性潜性パーキンソン病(PD)とミトコンドリアの関連が示唆されている。DJ-1は遺伝性潜性PDの原因因子であり、PD患者由来の変異によってミトコンドリアに移行する。しかしながら、DJ-1の分子機能や病態を導く機序には諸説あり、いまだに混沌としている。
我々は、DJ-1がα-オキソアルデヒドを加水してα-ヒドロキシ酸に変換することを示してきた。さらに研究を進める過程で、DJ-1の酵素活性を反映した「グリオキシル酸との結合」と「DJ-1のミトコンドリア移行」との予期せぬ関連性を見出した。本研究を通じて、DJ-1が遺伝性潜性PDを引き起こす仕組みの理解が進むと期待される。
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Report
(4 results)
Research Products
(32 results)
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[Journal Article] Cleaved PGAM5 dephosphorylates nuclear serine/arginine-rich proteins during mitophagy.2021
Author(s)
Baba, T., Tanimura, S., Yamaguchi, A., Horikawa, K., Yokozeki, M., Hachiya, S., Iemura, S., Natsume, T., Matsuda, N. and Takeda, K.
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Journal Title
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Volume: 11868
Issue: 7
Pages: 119045-119045
DOI
Related Report
Peer Reviewed
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[Journal Article] Unfolding is the driving force for mitochondrial import and degradation of the Parkinson's disease-related protein DJ-12021
Author(s)
Queliconi BB, Kojima W, Kimura M, Imai K, Udagawa C, Motono C, Hirokawa T, Tashiro S, Caaveiro JMM, Tsumoto K, Yamano K, Tanaka K, Matsuda N
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Journal Title
J Cell Sci
Volume: 134
Issue: 22
Pages: 1-1
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Endosomal Rab cycles regulate Parkin-mediated mitophagy.2018
Author(s)
Yamano K, Wang C, Sarraf SA, Münch C, Kikuchi R, Noda NN, Hizukuri Y, Kanemaki MT, Harper W, Tanaka K, Matsuda N, Youle RJ.
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Journal Title
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Structural insights into ubiquitin phosphorylation by PINK12018
Author(s)
Okatsu Kei、Sato Yusuke、Yamano Koji、Matsuda Noriyuki、Negishi Lumi、Takahashi Akiko、Yamagata Atsushi、Goto-Ito Sakurako、Mishima Masaki、Ito Yutaka、Oka Toshihiko、Tanaka Keiji、Fukai Shuya
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Journal Title
Scientific Reports
Volume: 8
Issue: 1
Pages: 10382-10382
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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