Activation of Atg7-dependent autophagy by a novel inhibitor of the Keap1–Nrf2 protein–protein interaction from <i>Penthorum chinense</i> Pursh. attenuates 6-hydroxydopamine-induced ferroptosis in zebrafish and dopaminergic neurons

Abstract

in the human neuroblastoma cell line SH-SY5Y. Th A degraded Keap1 protein through activating Atg7-dependent autophagy. Additionally, Th A treatment facilitated the degradation of Keap1 protein by promoting the interaction between p62/SQSTM1 (sequestosome 1, hereafter referred to as p62) and Keap1. Taken together, our findings indicated that Th A protects dopaminergic cells against 6-OHDA-induced ferroptosis through activating the Nrf2-based cytoprotective system, thus enabling a potential application of Keap1-Nrf2 PPI inhibitors in the restraint of ferroptosis and treatment of PD.