2. Academic Validation
  3. REV-ERBα inhibitor rescues MPTP/MPP+-induced ferroptosis of dopaminergic neuron through regulating FASN/SCD1 signaling pathway

REV-ERBα inhibitor rescues MPTP/MPP+-induced ferroptosis of dopaminergic neuron through regulating FASN/SCD1 signaling pathway

  • Heliyon. 2024 Nov 15;10(23):e40388. doi: 10.1016/j.heliyon.2024.e40388.
Xiaoyu Wang 1 2,  Mingmei Wang 3,  Hui Zhi 1,  Jingwei Li 1,  Dongkai Guo 1
Affiliations

Affiliations

  • 1 Department of Pharmacy, Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, 215153, China.
  • 2 Department of Pharmacy, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, 215002, China.
  • 3 College of Biological and Food Engineering, Changshu Institute of Technology, Changshu, 215500, China.
PMID: 39654780 DOI: 10.1016/j.heliyon.2024.e40388
Abstract

Circadian disruption is a risk factor for Parkinson's disease (PD). Ferroptosis, a cellular death process, assumes a pivotal role in the degeneration of dopaminergic neurons in PD. Despite its significance, the potential contribution of circadian clock proteins to PD through the modulation of Ferroptosis remains elusive. Our investigation unveiled a reduction in the circadian clock protein REV-ERBα in both MPTP/MPP+ and Ferroptosis models. REV-ERBα actively promotes Ferroptosis by binding to the RORE cis-element and suppressing the transcription of Fasn and Scd1, two genes that inhibit Ferroptosis. Notably, inhibiting REV-ERBα exhibited a discernible mitigating effect on Ferroptosis and the ensuing dopaminergic neuron damage induced by MPTP/MPP+. Consequently, targeting REV-ERBα emerges as a promising strategy for inhibiting Ferroptosis and presents a novel therapeutic avenue for PD.

Keywords

FASN; Ferroptosis; GPX4; REV-ERBα; SCD1.

Figures
Products