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Molecules 2017, 22(10), 1769; doi:10.3390/molecules22101769

α-Synuclein Regulates Neuronal Cholesterol Efflux

1
Brain and Mind Centre, Sydney Medical School, The University of Sydney, Sydney NSW 2050, Australia
2
Neuroscience Research Australia, Sydney NSW 2031, Australia
3
School of Medical Sciences, University of New South Wales, Sydney NSW 2052, Australia
*
Author to whom correspondence should be addressed.
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)
View Full-Text   |   Download PDF [1140 KB, uploaded 19 October 2017]   |  

Abstract

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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