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Title: | Therapeutics potentiating microglial p21-Nrf2 axis can rescue neurodegeneration caused by neuroinflammation |
Authors: | Nakano-Kobayashi, A. Fukumoto, A. Morizane, A. Nguyen, D. T. Le, T. M. Hashida, K. Hosoya, T. Takahashi, R. Takahashi, J. Hori, O. Hagiwara, M. |
Author's alias: | 小林, 亜希子 萩原, 正敏 |
Issue Date: | 11-Nov-2020 |
Publisher: | American Association for the Advancement of Science (AAAS) |
Journal title: | Science Advances |
Volume: | 6 |
Issue: | 46 |
Thesis number: | eabc1428 |
Abstract: | Neurodegenerative disorders are caused by progressive neuronal loss, and there is no complete treatment available yet. Neuroinflammation is a common feature across neurodegenerative disorders and implicated in the progression of neurodegeneration. Dysregulated activation of microglia causes neuroinflammation and has been highlighted as a treatment target in therapeutic strategies. Here, we identified novel therapeutic candidate ALGERNON2 (altered generation of neurons 2) and demonstrate that ALGERNON2 suppressed the production of proinflammatory cytokines and rescued neurodegeneration in a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)–induced Parkinson’s disease model. ALGERNON2 stabilized cyclinD1/p21 complex, leading to up-regulation of nuclear factor erythroid 2–related factor 2 (Nrf2), which contributes to antioxidative and anti-inflammatory responses. Notably, ALGERNON2 enhanced neuronal survival in other neuroinflammatory conditions such as the transplantation of induced pluripotent stem cell–derived dopaminergic neurons into murine brains. In conclusion, we present that the microglial potentiation of the p21-Nrf2 pathway can contribute to neuronal survival and provide novel therapeutic potential for neuroinflammation-triggered neurodegeneration. |
Description: | 神経炎症の抑制を可能にする新規化合物を発⾒ --iPS-ドパミン神経前駆細胞の移植を促進--. 京都大学プレスリリース. 2020-11-16. |
Rights: | © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
URI: | http://hdl.handle.net/2433/258964 |
DOI(Published Version): | 10.1126/sciadv.abc1428 |
PubMed ID: | 33188020 |
Related Link: | https://www.kyoto-u.ac.jp/ja/research-news/2020-11-16 |
Appears in Collections: | Journal Articles |
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