Interaction of alpha-synuclein and Parkin in iron toxicity on SH-SY5Y cells: implications in the pathogenesis of Parkinson's disease
Upasana Ganguly, Anindita Banerjee, Sankha Shubhra Chakrabarti, Upinder Kaur, Oishimaya Sen, Roberto Cappai, Sasanka Chakrabarti
Biochemical Journal | PORTLAND PRESS LTD | Published : 2020
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..View full abstract
Awarded by Department of Science and Technology, Government of India
The primary funding for this work was obtained from the Department of Science and Technology, Government of India (Sanction No. SR/SO/HS-026/2012) by Prof. Sasanka Chakrabarti.