Investigating the effects of α-synuclein variants on mitochondrial function in Parkinson’s disease

Abstract

Parkinson’s disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta region of the brain and affects millions of individuals worldwide each year. It is known that mitochondrial dysfunction and Lewy body formation are both associated with the disease, but the extent to which these two symptoms are related has yet to be determined. In this study, the effects of α-synuclein, the major protein component of Lewy bodies, on mitochondrial dysfunction was tested by cloning five different α-synuclein variants (each with differing aggregation and trafficking potentials) and expressing them in live human neuronal cell lines to determine if there was a significant decrease in mitochondrial health and function. The results suggested that all α-synuclein variants, including wildtype α-synuclein, decreased mitochondrial polarization, a measure of health and function. These data suggest that a more detailed investigation of α-synuclein expression and mitochondrial function is warranted.