Alpha-synuclein induced mitochondrial aberrations in a genetic cell culture model of Parkinson's disease

Abstract

Mutations in the α-synuclein encoding gene, SNCA, have been implicated in the pathophysiology and progression of Parkinson’s disease, a neurodegenerative disorder which results in motor and cognitive abnormalities in patients. Missense mutations, duplications and triplications of the gene relate to the onset and advancement of the ailment, but the role of α-synuclein protein in the pathogenesis is incompletely understood. Recent investigation of the disease and its other associated proteins has driven interest in the role of mitochondrial abnormalities in Parkinson’s disease. Through use of an ecdysone-inducible expression system in the mammalian neuronal cell line, 1RB3AN27, the detrimental effects of mutant A53T α-synuclein upon mitochondrial morphology has been established, which corroborates the work of similar studies. Complementary immunocytochemistry and western blot analyses allude to the time dependent increase in protein expression and the corresponding fragmentation of mitochondria. Analysis of mitochondrial function using Seahorse XFe24 technology proved inconclusive; further work is needed to confirm the consequences of mutant A53T α-synuclein expression upon mitochondrial respiratory capacity in this disease model.