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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
REVIEW
Cholesterol dysfunction in neurodegenerative diseases: is Huntington's disease in the list?
Progress in Neurobiology 2006 November
Brain cholesterol is an essential component of cell membranes, and involved in a number of biological functions such as membrane trafficking, signal transduction, myelin formation and synaptogenesis. Given these widespread activities and the knowledge that all brain cholesterol derives from local synthesis, it is not surprising that dysfunctions in cholesterol synthesis, storage, transport and removal may lead to human brain diseases. Some of these diseases emerge as a consequence of genetic defects in the enzymes involved in cholesterol biosynthesis; in other cases, such as Alzheimer's disease, there is a link between cholesterol metabolism and the formation and deposition of amyloid-beta peptide. Emerging evidence indicates that changes in cholesterol synthesis may also occur in Huntington's disease, an inherited, autosomal dominant neurodegenerative disorder that primarily affects striatal neurons of the brain. We here provide an overview of the involvement of cholesterol in normal brain function and its impact on neurodegenerative diseases. In particular, we consider the available clinical, biological and molecular evidence indicating a potential dysregulation of cholesterol homeostasis in Huntington's disease.
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