title: Alpha-synuclein impairs normal dynamics of mitochondria in cell and animal models of Parkinson's disease.
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.
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Weilin
authors.initials: W
authors.lastname: Xie
authors.forename: Kenny K K
authors.initials: KK
authors.lastname: Chung
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D059290:Dopaminergic Neurons / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000187:drug effects* / Q000648:ultrastructure; D009415:Nerve Net / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010302:Parkinson Disease, Secondary / Q000378:metabolism / Q000473:pathology*; D010957:Plasmids / Q000235:genetics; D013116:Spinal Cord / Q000378:metabolism; D014162:Transfection; D051844:alpha-Synuclein / Q000235:genetics* / Q000502:physiology*; D051846:beta-Synuclein / Q000494:pharmacology
chemical_list: D009419:Nerve Tissue Proteins; D051844:alpha-Synuclein; D051846:beta-Synuclein