| RRC ID |
78243
|
| 著者 |
Hamano S, Noguchi T, Asai Y, Ito R, Komatsu R, Sato T, Inoue A, Maruyama T, Kudo TA, Hirata Y, Shindo S, Uchida Y, Hwang GW, Matsuzawa A.
|
| タイトル |
Aggregability of the SQSTM1/p62-based aggresome-like induced structures determines the sensitivity to parthanatos.
|
| ジャーナル |
Cell Death Discov
|
| Abstract |
Overactivation of poly (ADP-ribose) polymerase-1 (PARP-1) triggers a noncanonical form of programmed cell death (PCD) called parthanatos, yet the mechanisms of its induction are not fully understood. We have recently demonstrated that the aggresome-like induced structures (ALIS) composed of the autophagy receptor SQSTM1/p62 and K48-linked polyubiquitinated proteins (p62-based ALIS) mediate parthanatos. In this study, we identified the D1 dopamine receptor agonist YM435 as a unique parthanatos inhibitor that acts as the disaggregating agent for the p62-based ALIS. We found that YM435 structurally reduces aggregability of the ALIS, and then increases its hydrophilicity and liquidity, which prevents parthanatos. Moreover, dopamine and L-DOPA, a dopamine precursor, also prevented parthanatos by reducing the aggregability of the ALIS. Together, these observations suggest that aggregability of the p62-based ALIS determines the sensitivity to parthanatos, and the pharmacological properties of YM435 that reduces the aggregability may be suitable for therapeutic drugs for parthanatos-related diseases such as neurodegenerative diseases.
|
| 巻・号 |
10(1)
|
| ページ |
74
|
| 公開日 |
2024-2-12
|
| DOI |
10.1038/s41420-024-01838-2
|
| PII |
10.1038/s41420-024-01838-2
|
| PMID |
38346947
|
| PMC |
PMC10861449
|
| リソース情報 |
| ヒト・動物細胞 |
PC-12(RCB0009) |
