KIF5A inhibition ferroptosis in Parkinson's disease

Abstract

Abstract Parkinson's disease (PD) is a highly prevalent neurodegenerative disorder associated with abnormal brain iron metabolism. Ferroptosis is a newly discovered form of iron-dependent cell death. In recent years, many studies have identified ferroptosis as an important pathogenic mechanism of PD. Nevertheless, the underlying mechanisms remain unclear. A 6-hydroxydopamine (6-OHDA) stimulated the PD rat model and the PD cell model were used in this research. The experimental results showed that the level of kinesin 1 heavy chain (KIF5A) decreases, and the level of ferroptosis increases after 6-OHDA stimulation. A PD cell model is consistent with these results. The overexpression of KIF5A in SH-SY5Y cells significantly reduces intracellular lipid peroxidation, Fe2+ accumulation, and ferroptosis. In contrast, knockdown of KIF5A exacerbated lipid peroxidation and Fe2+ accumulation, and cellular ferroptosis was more severe. Therefore, this study provides new views and potential for studying treatment targets of PD by demonstrating that KIF5A protects cells from ferroptosis in a PD model.