Soman induces endoplasmic reticulum stress and apoptosis of cerebral organoids via the GRP78-ATF6-CHOP signaling pathway.

ABSTRACT: Soman is an organophosphorus compound that induces neurotoxicity. In addition to its direct toxic effects resulting from acetylcholine accumulation, neurotoxicity may also be exacerbated by inducing endoplasmic reticulum (ER) stress. In light of the current scarcity of appropriate in vitro assessment models, in the present study, we used cerebral organoids derived from human pluripotent stem cells, a new tool for investigating the mechanisms of neurotoxicity, to investigate soman-induced ER stress. The results demonstrated that soman significantly suppressed acetylcholinesterase activity and activated the GRP78-ATF6-CHOP (i.e. glucose-regulated protein 78-activating transcription factor 6-C/EBP homologous protein) ER stress cascade, driving apoptosis in cerebral organoids. Pharmacological

SUBMITTER: Wei Y 

PROVIDER: S-EPMC12226415 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature