Main > NEUROLOGY. > Alzheimer's Disease > Treatment > Cholesterol. Connection > ACAT Inhibitors. > Org.: USA. H (CP-113,818/Study) > NPLS Contents

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Researchers are trying to get a clearer picture of these interactions by studying another class of drugs that affect cholesterol. Known as ACAT inhibitors, the drugs block acyl-coenzymeA:cholesterol acyltransferase (ACAT), an enzyme that regulates cholesterol distribution. Some of these inhibitors, such as avasimibe, are in clinical trials to treat cardiovascular disease. In addition, avasimibe and another ACAT inhibitor--CP-113,818, which is a fatty acid anilide derivative--are being studied in the lab as a therapy for Alzheimer s.

ACAT normally converts cholesterol located in cell membranes into a form that is stored in intracellular droplets for later use. When ACAT s active site is blocked, less cholesterol is stored.

In 2001, Author, and colleagues showed that ACAT also regulates the formation of amyloid- in cell culture. In more recent work, she showed that inhibiting ACAT with CP-113,818 virtually eliminates amyloid pathology in a mouse model of Alzheimer s disease.

Furthermore, "we found that this way of reducing cholesterol levels in the brains of living animals improved learning," Author adds. "As far as we know, this is the first study of cholesterol metabolism s impact on amyloid levels that included cognitive testing."

Analysis of brain tissue from the mice in the trial leads Author to believe that the ACAT inhibitor lowers production of amyloid- rather than reducing its deposition. Author and her team are now studying the effect of avasimibe on amyloid-.




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