Premium
Effects of the cholesterol‐lowering compound methyl‐β‐cyclodextrin in models of α‐synucleinopathy
Author(s) -
BarOn Pazit,
Rockenstein Edward,
Adame Anthony,
Ho Gilbert,
Hashimoto Makoto,
Masliah Eliezer
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04017.x
Subject(s) - synucleinopathies , alpha synuclein , context (archaeology) , cholesterol , dementia with lewy bodies , alpha (finance) , lewy body , biochemistry , chemistry , biology , microbiology and biotechnology , parkinson's disease , medicine , dementia , disease , paleontology , construct validity , nursing , patient satisfaction
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.