Alpha-synuclein impairs normal dynamics of mitochondria in cell and animal models of Parkinson's disease - PubMed (original) (raw)

. 2012 Jul;122(2):404-14.

doi: 10.1111/j.1471-4159.2012.07769.x. Epub 2012 May 23.

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• PMID: 22537068
• DOI: 10.1111/j.1471-4159.2012.07769.x

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Alpha-synuclein impairs normal dynamics of mitochondria in cell and animal models of Parkinson's disease

Weilin Xie et al. J Neurochem. 2012 Jul.

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Abstract

Alpha-synuclein (α-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 pars compacta (SNc). How α-syn can contribute to neurodegeneration in PD is not conclusive but it is agreed that mutations or excessive accumulation of α-syn can lead to the formation of α-syn oligomers or aggregates that interfere with normal cellular function and contribute to the degeneration of dopaminergic neurons. In this study, we found that α-syn can impair the normal dynamics of mitochondria and this effect is particular prominent in A53T α-syn mutant. In mice expressing A53T α-syn, age-dependent changes in both mitochondrial morphology and proteins that regulate mitochondrial fission and fusion were observed. In the cellular model of PD, we found that α-syn reduces the movement of mitochondria in both SH-SY5Y neuroblastoma and hippocampal neurons. Taken together, our study provides a new mechanism of how α-syn can contribute to PD through the impairment of normal dynamics of mitochondria.

© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

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