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 |
Section | 一般 |
Review Section |
Basic Section 44010:Cell biology-related
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Research Institution | Tokyo Metropolitan Institute of Medical Science |
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 |
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
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
Pages: 1-1
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Parkin-mediated ubiquitylation redistributes MITOL/March5 from mitochondria to peroxisomes.2019
Author(s)
Koyano, F., Yamano, K., Kosako, H., Kimura, K., Kimura, M., Fujiki, Y., Tanaka, K., and Matsuda, N.
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Journal Title
DOI
NAID
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, S. A., Munch, C., Kikuchi, R., Noda, N. N., Hizukuri, Y., Kanemaki, M. T., Harper, W., Tanaka, K., Matsuda, N., and Youle, R. J.
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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 PINKI.2018
Author(s)
Okatsu, K., Sato, Y., Yamano, K., Matsuda, N., Negishi, L., Takahashi, A., Yamagata, A., Goto-Ito, S., Mishima, M., Ito, Y., Oka, T., Tanaka, K., and Fukai, S.
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Journal Title
Sci. Rep.
Volume: 8
Pages: 10382-10382
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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