Investigation of the relationship of HSP27 inhibitor J2 molecule with ferroptosis in in vitro Parkinson's disease model

Heat shock protein 27 (HSP27) is a chaperone protein whose expression level increases under cellular stress conditions. Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron loss and the accumulation of α-synuclein protein aggregates, which parallel the decreased activity of heat shock proteins (HSPs). Ferroptosis is a cell death pathway triggered by iron accumulation and lipid peroxidation, and its association with PD has been established. In this study, the ferroptotic and apoptotic effects of the HSP27 inhibitor J2 molecule, which has been investigated for its use in various cancer types, were examined in an in vitro PD model induced by rotenone. Different concentrations of the J2 molecule were applied to the SH-SY5Y cell line and a rotenone-induced PD model derived from this cell line, and cell viability percentages were determined. Apoptotic and pro-apoptotic protein/mRNA levels were analyzed to investigate apoptotic processes. The translational and post-translational levels of HSP27 were examined using Western-blot analysis and a luciferase aggregation assay. Furthermore, ferroptotic effects were assessed by determining the Fe²/Fe³ ratio, antioxidant-oxidant balance, malondialdehyde levels, and GPx4 levels in the cell groups. It was determined that J2-mediated inhibition of HSP27 negatively affected cellular survival and activated both apoptotic and ferroptotic pathways.