17β-estradiol alleviated ferroptotic neuroinflammation by suppressing ATF4 in mouse model of Parkinson's disease.

ABSTRACT: Neuroinflammation induced by activation of microglial is a vital contributor to progression of Parkinson's disease (PD), emerging evidences suggested that ferroptosis played a pivotal role in microglial activation and subsequent dopaminergic neuron loss. Nevertheless, the fundamental pathogenesis of that ferroptosis contributes to PD is not yet sufficiently understood. Based on GEO dataset, ferroptosis related genes were found to be enriched in PD patients and MPTP mouse model of PD, among them, ATF4 was found to be dramatically differentially expressed. In our study, ectopic expression of ATF4 augmented MPP⁺-induced cytotoxic and activation of BV2 cells with upregulated intracellular L-ROS, TLR4 and pNF-κB. Ectopic ATF4 effectively promoted transformation of microglial into M1

SUBMITTER: Wang G 

PROVIDER: S-EPMC11659321 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature