Recent advances on alpha-synuclein cell biology: functions and dysfunctions.
Alpha-synuclein is a recently discovered protein that was first identified as the major non amyloid component of senile plaques, the cerebral lesion likely responsible for Alzheimer's disease. The role of alpha-synuclein in another brain disease namely Parkinson's disease, has been more deeply documented. It appears that alpha-synuclein fills up the intracytoplasmic inclusions called Lewy bodies that likely contribute to the etiology of Parkinson's disease. Furthermore, rare familial forms of Parkinson's disease have been shown to be linked to autosomal dominant mutations of alpha-synucleins. Is alpha-synuclein a bridge between Alzheimer's and Parkinson's diseases? Could it be seen as a common denominator for these two neurodegenerative diseases? These issues could be better addressed by further delineating the physiological function of alpha-synuclein and, as a corollary, the dysfunction taking place along with the diseases. Here, I will review the recent advances concerning the physiology of alpha-synuclein and will particularly focus on the post-traductional events leading to drastic biophysical transformations. I will describe recent works suggesting that these modifications directly modulate the normal function of alpha-synuclein, likely accounting for the dysfunction associated with Parkinson's disease and perhaps contributing to Alzheimer's pathology.
Alves da Costa
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IPMC du CNRS, UMR6097, 660 Route des Lucioles, Sophia Antipolis, 06560, Valbonne, France. acosta@ipmc.cnrs.fr
D000544:Alzheimer Disease / Q000209:etiology; D000818:Animals; D001921:Brain / Q000502:physiology*; D016923:Cell Death / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009473:Neuronal Plasticity; D010300:Parkinson Disease / Q000209:etiology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000502:physiology; D051843:Synucleins; D022161:Transport Vesicles / Q000502:physiology; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; C497605:Snca protein, mouse; D051843:Synucleins; D051844:alpha-Synuclein