| Parkinson's disease (PD) is a progressive movement disorder marked by a selective dopaminergic neuronal loss in the brain stem and the presence of protein aggregates designated as Lewy bodies (LBs). The cause of most PD cases is not known but a small percentage of patients are known to inherit the disease from the family. Alpha-synuclein (alpha-syn) is a synaptic protein that mutations have been linked to Parkinson's disease (PD), a common neurodegenerative disorder that is caused by the degeneration of the dopaminergic neurons in the substantia nigra (SNc). How alpha-syn can contribute to neurodegeneration in PD is not conclusive but it is agreed that mutations or excessive accumulation of alpha-syn can lead to the formation of alpha-syn oligomers or aggregates that interfere with normal cellular function and contribute to the degeneration of dopaminergic neurons. In this study, we found that alpha-syn can impair the normal dynamics of mitochondria and this effect is particular prominent in A53T alpha-syn mutant. In the cellular model of PD, we found that alpha-syn reduces the movement of mitochondria in both SH-SHY5Y neuroblastoma and in hippocampal neurons. In mice expressing A53T alpha-syn, age-dependent changes in both mitochondrial morphology and proteins that regulate mitochondrial fission and fusion were observed. Taken together, our study provides a new mechanism of how alpha-syn can contribute to PD through the impairment of normal dynamics of mitochondria. |
