REV-ERBα inhibitor rescues MPTP/MPP+-induced ferroptosis of dopaminergic neuron through regulating FASN/SCD1 signaling pathway
Xiaoyu Wang,
Mingmei Wang,
Hui Zhi,
Jingwei Li,
Dongkai Guo
Affiliations
Xiaoyu Wang
Department of Pharmacy, Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, 215153, China; Department of Pharmacy, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, 215002, China
Mingmei Wang
College of Biological and Food Engineering, Changshu Institute of Technology, Changshu, 215500, China
Hui Zhi
Department of Pharmacy, Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, 215153, China
Jingwei Li
Department of Pharmacy, Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, 215153, China; Corresponding author.
Dongkai Guo
Department of Pharmacy, Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, 215153, China; Corresponding author.
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.
