Propofol addiction drives neuronal senescence and cognitive decline via autophagy-mediated ADAR1/SIRT1 disruption.

ABSTRACT: Propofol addiction represents a significant clinical challenge with no approved pharmacotherapy. While cognitive decline is a hallmark of substance use disorders, its underlying mechanisms in propofol addiction remain unclear. This study investigates whether propofol abuse induces neuronal senescence and cognitive impairment and explores the involved molecular pathways. We found that propofol administration in mice led to significant learning and memory deficits, which were associated with p16^INK4a-dependent neuronal senescence in the hippocampus. Knockdown of p16^INK4a alleviated both senescence and cognitive decline. Mechanistically, propofol triggered autophagic degradation of ADAR1 via LC3-binding motifs, leading to reduced SIRT1 expression and subsequent upregulat

SUBMITTER: Wang X 

PROVIDER: S-EPMC12749188 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature