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- Title
α-Synuclein Regulates Neuronal Cholesterol Efflux.
- Authors
Hsiao, Jen-Hsiang T.; Halliday, Glenda M.; Woojin Scott Kim
- 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.
- Subjects
PARKINSON'S disease; SYNUCLEINS; NEURODEGENERATION; CARRIER proteins; NERVE tissue proteins
- Publication
Molecules, 2017, Vol 22, Issue 10, p1769
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules22101769