RRC ID |
78243
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Author |
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.
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Title |
Aggregability of the SQSTM1/p62-based aggresome-like induced structures determines the sensitivity to parthanatos.
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Journal |
Cell Death Discov
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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.
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Volume |
10(1)
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Pages |
74
|
Published |
2024-2-12
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DOI |
10.1038/s41420-024-01838-2
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PII |
10.1038/s41420-024-01838-2
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PMID |
38346947
|
PMC |
PMC10861449
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Resource |
Human and Animal Cells |
PC-12(RCB0009) |