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Nuclear SOD1 links ATM-CHK2 signaling to ADH5/GSNOR transcription in SHSY-5Y SOD1G93A cellular models of ALS

TitleNuclear SOD1 links ATM-CHK2 signaling to ADH5/GSNOR transcription in SHSY-5Y SOD1G93A cellular models of ALS
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2026
AuthorsPecorari, Chiara, Montagna Costanza, Cozzolino Mauro, D'Ambrosi Nadia, Benassi Barbara, Cirotti Claudia, and Filomeni Giuseppe
JournalNitric Oxide - Biology and Chemistry
Volume164
Pagination69 - 74
Type of ArticleArticle
ISSN10898603
Abstract

The activity of S-nitrosoglutathione reductase (ADH5/GSNOR) has been proposed being essential to limit oxidative stress and preserve mitochondrial quality control. Here we identify a redox-dependent ATM-CHK2-SOD1 signaling axis that drives ADH5/GSNOR transcription in SH-SY5Y cells expressing the ALS-associated SOD1G93A mutant. ATM-CHK2 activation promotes the interaction of SOD1 with CHK2, leading to SOD1 nuclear translocation and binding to the ADH5 promoter. Pharmacological inhibition of ATM or CHK2 abolishes these effects. ADH5/GSNOR overexpression protects cells from SOD1G93A-induced toxicity suggesting that the modulation of GSNOR activity may represent a potential strategy to restore redox homeostasis in ALS. © 2026 Elsevier Inc.

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URLhttps://www.scopus.com/pages/publications/105047064890?origin=resultslist
DOI10.1016/j.niox.2026.08.001
Citation KeyPecorari202669