Apoptosis. 2026 Apr 6;31(4):120. doi: 10.1007/s10495-026-02326-x.
ABSTRACT
Early-life exposure to general anesthetics, particularly propofol, elevates the risk of neurodevelopmental impairment and cognitive sequelae in pediatric populations, representing a pivotal concern in translational neuroanesthesiology. Although preclinical studies have linked propofol to increased developmental neurotoxicity, the underlying molecular mechanisms remain elusive. Our previous work established that nuclear fragile X mental retardation-interacting protein 1 (NUFIP1)-engineered exosomes from human umbilical cord mesenchymal stem cells could mitigate propofol-induced neurotoxicity and neuronal apoptosis in neonatal rats during a critical postnatal window of synaptogenesis (postnatal days 7-14). The present study provides the first mechanistic insights by performing transcriptomic profiling to link this neuroprotection to the endoplasmic reticulum stress (ERS) apoptotic pathway. Importantly, we directly validated key ERS/apoptosis markers and functionally confirmed the pathway’s role through pharmacological rescue experiments with Salubrinal. In conclusion, NUFIP1-engineered exosomes regulate propofol-induced nerve injury through the ERS apoptotic pathway, offering novel mechanistic insights with potential implications for addressing pediatric neurodevelopmental impairments.
PMID:41942784 | DOI:10.1007/s10495-026-02326-x
