CO confers neuroprotection via activating the PERK-calcineurin pathway and inhibiting necroptosis.

ABSTRACT: Neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD), are marked by progressive neuronal loss. Regulated cell death programs (i.e., necroptosis) as well as homeostatic mechanisms (i.e., autophagy) can modulate disease pathogenesis. Low-dose carbon monoxide (CO) has been shown to activate cytoprotective responses in various models of tissue injury. Our study investigates the protective roles of CO in neurodegenerative disease through the modulation of necroptosis and autophagy programs. We found that CO activates the Protein kinase RNA (PKR)-like ER kinase (PERK) branch of the unfolded protein response (UPR) and the calcineurin pathway, leading to significant neuroprotective effects in cellular and mouse models of PD. CO-induced PERK activation promotes

SUBMITTER: Park J 

PROVIDER: S-EPMC12116729 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature