Affiliation:
1. Department of Neurosurgery The Affiliated Hospital of Northwest University Xi'an China
Abstract
AbstractEmerging evidence has suggested that N6‐methyladenosine (m6A) regulates the pathology of Parkinson's disease (PD). Nevertheless, the function of demethylase fat mass and obesity (FTO) associated pathogenesis is still not fully elucidated. Here, this research findings revealed that m6A‐modification was decreased in PD models, meanwhile, the FTO level upregulated in the PD models. Functionally, in N‐methyl‐4‐phenylpyridinium (MPP+) treated SH‐SY5Y cells, the ferroptosis significantly upregulated and FTO silencing mitigated the ferroptosis phenotype. Moreover, in silico assays indicated that nuclear factor erythroid 2‐related factor‐2 (NRF2) acted as the target of FTO, and FTO demethylated the m6A modification from NRF2 mRNA. Furthermore, FTO impaired the NRF2 mRNA stability via m6A‐dependent pathway. Thus, our findings illustrated an important role of FTO on PD through m6A‐NRF2‐ferroptosis manner. Taken together, the study revealed the potential function of FTO on PD nervous system diseases.
Subject
Cell Biology,General Medicine