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Open AccessArticle

α-Synuclein Regulates Neuronal Cholesterol Efflux

Brain and Mind Centre, Sydney Medical School, The University of Sydney, Sydney NSW 2050, Australia
Neuroscience Research Australia, Sydney NSW 2031, Australia
School of Medical Sciences, University of New South Wales, Sydney NSW 2052, Australia
Author to whom correspondence should be addressed.
Molecules 2017, 22(10), 1769;
Received: 26 September 2017 / Revised: 18 October 2017 / Accepted: 19 October 2017 / Published: 19 October 2017
(This article belongs to the Special Issue Neuroprotective Agents)
α-Synuclein is a neuronal protein that is at the center of focus in understanding the etiology of a group of neurodegenerative diseases called α-synucleinopathies, which includes Parkinson’s disease (PD). Despite much research, the exact physiological function of α-synuclein is still unclear. α-Synuclein has similar biophysical properties as apolipoproteins and other lipid-binding proteins and has a high affinity for cholesterol. These properties suggest a possible role for α-synuclein as a lipid acceptor mediating cholesterol efflux (the process of removing cholesterol out of cells). To test this concept, we “loaded” SK-N-SH neuronal cells with fluorescently-labelled cholesterol, applied exogenous α-synuclein, and measured the amount of cholesterol removed from the cells using a classic cholesterol efflux assay. We found that α-synuclein potently stimulated cholesterol efflux. We found that the process was dose and time dependent, and was saturable at 1.0 µg/mL of α-synuclein. It was also dependent on the transporter protein ABCA1 located on the plasma membrane. We reveal for the first time a novel role of α-synuclein that underscores its importance in neuronal cholesterol regulation, and identify novel therapeutic targets for controlling cellular cholesterol levels. View Full-Text
Keywords: α-synuclein; cholesterol efflux; ABCA1; apolipoproteins; Parkinson’s disease α-synuclein; cholesterol efflux; ABCA1; apolipoproteins; Parkinson’s disease
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Hsiao, J.-H.T.; Halliday, G.M.; Kim, W.S. α-Synuclein Regulates Neuronal Cholesterol Efflux. Molecules 2017, 22, 1769.

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