ID | 66946 |
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Author |
Murata, Hitoshi
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Phoo, May Tha Zin
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ochi, Toshiki
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Tomonobu, Nahoko
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yamamoto, Ken-ichi
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kinoshita, Rie
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Miyazaki, Ikuko
Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Nishibori, Masahiro
Department of Translational Research and Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Asanuma, Masato
Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Sakaguchi, Masakiyo
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Abstract | Sterile alpha and Toll/interleukin receptor motif-containing protein 1 (SARM1) is a NAD+ hydrolase that plays a key role in axonal degeneration and neuronal cell death. We reported that c-Jun N-terminal kinase (JNK) activates SARM1 through phosphorylation at Ser-548. The importance of SARM1 phosphorylation in the pathological process of Parkinson’s disease (PD) has not been determined. We thus conducted the present study by using rotenone (an inducer of PD-like pathology) and neurons derived from induced pluripotent stem cells (iPSCs) from healthy donors and a patient with familial PD PARK2 (FPD2). The results showed that compared to the healthy neurons, FPD2 neurons were more vulnerable to rotenone-induced stress and had higher levels of SARM1 phosphorylation. Similar cellular events were obtained when we used PARK2-knockdown neurons derived from healthy donor iPSCs. These events in both types of PD-model neurons were suppressed in neurons treated with JNK inhibitors, Ca2+-signal inhibitors, or by a SARM1-knockdown procedure. The degenerative events were enhanced in neurons overexpressing wild-type SARM1 and conversely suppressed in neurons overexpressing the SARM1-S548A mutant. We also detected elevated SARM1 phosphorylation in the midbrain of PD-model mice. The results indicate that phosphorylated SARM1 plays an important role in the pathological process of rotenone-induced neurodegeneration.
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Keywords | JNK
PARK2
Parkinson’sdisease
Phosphorylation
SARM1
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Published Date | 2023-09-19
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Publication Title |
The Journal of Biochemistry
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Volume | volume174
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Issue | issue6
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Publisher | Oxford University Press (OUP)
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Start Page | 533
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End Page | 548
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ISSN | 0021-924X
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NCID | AA00694073
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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Copyright Holders | © The Author(s) 2023.
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File Version | publisher
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Related Url | isVersionOf https://doi.org/10.1093/jb/mvad068
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License | https://creativecommons.org/licenses/by/4.0/
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Citation | Hitoshi Murata, May Tha Zin Phoo, Toshiki Ochi, Nahoko Tomonobu, Ken-ichi Yamamoto, Rie Kinoshita, Ikuko Miyazaki, Masahiro Nishibori, Masato Asanuma, Masakiyo Sakaguchi, Phosphorylated SARM1 is involved in the pathological process of rotenone-induced neurodegeneration, The Journal of Biochemistry, Volume 174, Issue 6, December 2023, Pages 533–548, https://doi.org/10.1093/jb/mvad068
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Funder Name |
Japan Society for the Promotion of Science
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助成番号 | 22K06884
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