Format

Send to

Choose Destination
Molecules. 2017 Oct 19;22(10). pii: E1769. doi: 10.3390/molecules22101769.

α-Synuclein Regulates Neuronal Cholesterol Efflux.

Hsiao JT1,2,3, Halliday GM4,5,6, Kim WS7,8,9.

Author information

1
Brain and Mind Centre, Sydney Medical School, The University of Sydney, Sydney NSW 2050, Australia. tony.hsiao@sydney.edu.au.
2
Neuroscience Research Australia, Sydney NSW 2031, Australia. tony.hsiao@sydney.edu.au.
3
School of Medical Sciences, University of New South Wales, Sydney NSW 2052, Australia. tony.hsiao@sydney.edu.au.
4
Brain and Mind Centre, Sydney Medical School, The University of Sydney, Sydney NSW 2050, Australia. glenda.halliday@sydney.edu.au.
5
Neuroscience Research Australia, Sydney NSW 2031, Australia. glenda.halliday@sydney.edu.au.
6
School of Medical Sciences, University of New South Wales, Sydney NSW 2052, Australia. glenda.halliday@sydney.edu.au.
7
Brain and Mind Centre, Sydney Medical School, The University of Sydney, Sydney NSW 2050, Australia. woojin.kim@sydney.edu.au.
8
Neuroscience Research Australia, Sydney NSW 2031, Australia. woojin.kim@sydney.edu.au.
9
School of Medical Sciences, University of New South Wales, Sydney NSW 2052, Australia. woojin.kim@sydney.edu.au.

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.

KEYWORDS:

ABCA1; Parkinson’s disease; apolipoproteins; cholesterol efflux; α-synuclein

PMID:
29048372
PMCID:
PMC6151759
DOI:
10.3390/molecules22101769
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center