Effects of the cholesterol-lowering compound methyl-β-cyclodextrin in models of α-synucleinopathy
Article first published online: 20 JUL 2006
Journal of Neurochemistry
Volume 98, Issue 4, pages 1032–1045, August 2006
How to Cite
Bar-On, P., Rockenstein, E., Adame, A., Ho, G., Hashimoto, M. and Masliah, E. (2006), Effects of the cholesterol-lowering compound methyl-β-cyclodextrin in models of α-synucleinopathy. Journal of Neurochemistry, 98: 1032–1045. doi: 10.1111/j.1471-4159.2006.04017.x
- Issue published online: 20 JUL 2006
- Article first published online: 20 JUL 2006
- Received February 10, 2006; revised manuscript received March 15, 2006; accepted March 15, 2006.
- lipid rafts;
- Parkinson's disease;
The aggregation of α-synuclein (α-syn) is believed to play a critical role in the pathogenesis of disorders such as dementia with Lewy bodies and Parkinson's disease. The function of α-syn remains unclear, although several lines of evidence suggest that α-syn is involved in synaptic vesicle trafficking, probably via lipid binding, and interactions with lipids have been shown to regulate α-syn aggregation. In this context, the main objective of this study was to determine whether methyl-β-cyclodextrin (MβCD), a cholesterol-extracting agent, interfered with α-syn accumulation in models of synucleinopathy. For this purpose, we studied the effects of MβCD on the accumulation of α-syn in a transfected neuronal cell line and in transgenic mice. Immunoblot analysis showed that MβCD reduced the level of α-syn in the membrane fraction and detergent-insoluble fraction of transfected cells. In agreement with the in vitro studies, treatment of mice with MβCD resulted in decreased levels of α-syn in membrane fractions and reduced accumulation of α-syn in the neuronal cell body and synapses. Taken together, these results suggest that changes in cholesterol and lipid composition using cholesterol-lowering agents may be used as a tool for the treatment of synucleinopathies.