| RRC ID |
76910
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| 著者 |
Murata H, Phoo MTZ, Ochi T, Tomonobu N, Yamamoto KI, Kinoshita R, Miyazaki I, Nishibori M, Asanuma M, Sakaguchi M.
|
| タイトル |
Phosphorylated SARM1 is involved in the pathological process of rotenone-induced neurodegeneration.
|
| ジャーナル |
J Biochem
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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.
|
| 公開日 |
2023-9-19
|
| DOI |
10.1093/jb/mvad068
|
| PII |
7277339
|
| PMID |
37725528
|
| IF |
2.476
|
| リソース情報 |
| ヒト・動物細胞 |
201B7(HPS0063)
585A1(HPS0354) |
