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Acyl-coenzyme A (CoA):cholesterol acyltransferases (ACATs), EC 220.127.116.11, are integral membrane proteins that catalyze the conversion of cholesterol to cholesteryl esters. ACATs have been implicated in the pathology of atherosclerosis and Alzheimer's disease.
Acyl-coenzyme (CoA):cholesterol acyltransferases (ACATs), EC 18.104.22.168, are integral membrane proteins that belong to the membrane bound O-acyl transferase (MBOAT) family. Two ACAT isoforms have been identified to date, ACAT1 and ACAT2, both of which are important for cholesterol homeostasis in normal tissues.
ACATs are expressed at low levels in the membrane of the endoplasmic reticulum. ACAT1 has almost ubiquitous tissue expression, being expressed in macrophages, liver hepatocytes and neurons, amongst others. In contrast ACAT2 has a more limited expression profile, although it is also expressed in macrophages and hepatocytes, albeit at lower levels. ACATs catalyze the conversion of excess cholesterol to cholesteryl esters (CEs). Cholesterol itself determines the activity of ACAT1, with increases and reductions in cholesterol levels resulting in enhanced or suppressed ACAT1 activity, respectively. Certain factors can also regulate ACAT1 gene expression, for example interferon-γ, urotensin-II and dexamethasone enhance ACAT1 expression, whereas ACAT1 is downregulated by adiponectin.
The upregulation of ACAT1 expression and the chronic accumulation of CE is associated with the formation of foamy macrophages and the onset and progression of atherosclerosis. Therefore the ACATs have been identified as a potential antiatherosclerotic therapeutic target. Inhibition of ACAT has been shown to reduce atherosclerotic plaque CE content and cause plaque regression in vivo. Furthermore ACAT could be a potential target for the treatment of Alzheimer's disease (AD). ACAT inhibition reduced amyloid plaque density in a mouse model of AD, although the exact mechanism is yet to be determined.
Tocris offers the following scientific literature for Acyl-CoA:Cholesterol Acyltransferase to showcase our products. We invite you to request* your copy today!
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Alzheimer's disease (AD) is a degenerative brain disease and the most common cause of dementia, affecting approximately 47 million people worldwide. Updated in 2015, this poster summarizes the structural and functional changes observed in the progression of this neurodegenerative disease, as well as classic AD drug targets.
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