Ferulic acid activates Nrf2/HO-1 signaling axis to ameliorate neuronal Golgi stress by SKP2.

BACKGROUND Traumatic brain injury (TBI) ranks among the top contributors to neurological impairments worldwide, with Golgi stress implicated in neuronal injury. This study investigated the neuroprotective effects of ferulic acid (FA) in TBI by regulating Golgi stress. METHODS HT-22 and NSC34 cells were exposed to H2O2 to induce a neuronal injury model. Protein expression were evaluated via Western blot and immunofluorescence. Cell viability and apoptosis were quantified using CCK-8 assay and TUNEL staining, respectively. The interactions between Src, SKP2, and Nrf2 were detected by Co-IP assay. RESULTS FA treatment reduced LDH release, as well as repressed Golgi stress and apoptosis by H2O2-induced in HT-22 and NSC34 cells. Mechanistically, FA inhibited Src-mediated phosphorylation of SKP2 at Y131, preventing SKP2-mediated Nrf2 ubiquitination and degradation. Moreover, FA activated the antioxidative Nrf2/HO-1 pathway, alleviating H2O2-induced Golgi stress and neuronal injury. CONCLUSION FA reduced neuronal Golgi stress in H2O2-treated neuronal cells by restoring the Nrf2/HO-1 signaling through inhibiting Src-mediated SKP2 phosphorylation. These findings indicate that FA is a potential neuroprotective agent.

• Publication year

  2026

• Venue

  Journal of Pharmacological Sciences

• Publication date

  2026-01-01

• Fields of study

  Medicine, Environmental Science

• Identifiers
  DOI 10.1016/j.jphs.2026.01.006PMID 41795959
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

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