Clusterin Inhibits Neuronal Ferroptosis via the PI3K-AKT-mTOR-SREBP1 Axis to Promote Functional Recovery after Spinal Cord Injury.

ABSTRACT: Neuronal ferroptosis is considered as a key mechanism contributing to neurological deficits during the secondary injury phase following spinal cord injury (SCI). Clusterin (CLU), a stress-responsive protein, has been reported to exert neuroprotective effects and promote neuronal survival in central nervous system injuries. However, its specific role in neuronal ferroptosis remains unclear. Here, we demonstrate that both exogenous recombinant CLU protein and endogenous CLU overexpression significantly inhibit neuronal ferroptosis, as evidenced by reduced lipid peroxidation, decreased iron accumulation, preserved mitochondrial integrity, and modulation of ferroptosis-related genes (upregulation of GPX4/xCT and downregulation of ACSL4). Mechanistically, CLU activates the PI3K-AKT-mTOR pathway

SUBMITTER: Yao S 

PROVIDER: S-EPMC12905574 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature