Interaction of alpha-synuclein and Parkin in iron toxicity on SH-SY5Y cells: implications in the pathogenesis of Parkinson's disease

Abstract

The toxicity of accumulated α-synuclein plays a key role in the neurodegeneration of Parkinson's disease. This study has demonstrated that iron in varying concentrations (up to 400 µM) causes an increase in α-synuclein content in SH-SY5Y cells associated with mitochondrial depolarization, decreased cellular ATP content and loss of cell viability during incubation up to 96 h. Knocking-down α-synuclein expression prevents cytotoxic actions of iron, which can also be prevented by cyclosporine A (a blocker of mitochondrial permeability transition pore). These results indicate that iron cytotoxicity is mediated by α-synuclein acting on mitochondria. Likewise siRNA mediated knock-down of Parkin ca..