Ziba Dehghani - Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
Ali Akbar Saboury - Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
Ali Akbar Meratan - Department of Biological Sciences, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, Iran

Recent studies suggest that accumulation of alpha-synuclein amyloid aggregates on mitochondria is associated with Parkinson disease and other Lewy body disorders. Clearly, these amyloid aggregates disrupt mitochondrial function and initiate a pathophysiological cascade leading to neuronal degeneration. However, the molecular mechanism(s) of alpha-synuclein toxicity and its effect on mitochondria, in particular, remain elusive. Hexokinase 1 (HK 1) is a key glycolytic enzyme that plays important roles by reducing mitochondrial reactive oxygen species (ROS) generation and preventing apoptosis in neurons and other cell types .In this study, we have investigated the effect of alpha-synuclein amyloid intermediates on the release of HK1 from rat brain mitochondria. We found that alpha-synuclein amyloid intermediates, including oligomer, protofibril, and mature fibril, triggered HK 1 detachment from mitochondrial membrane in a dose-dependent manner. Moreover, a significant decrease in HK 1 activity was observed upon addition of alpha-synuclein aggregates. Based on obtained results, we suggest that inactivation and detachment of HK 1 from mitochondrial membrane by alpha-synuclein aggregates may play important roles in oxidative stress and neurodegeneration of Parkinson disease.

α-synuclein, protein aggregation, mitochondria, hexokinase 1, Parkinson disease