Knockdown of ACAT-1 reduces amyloidogenic processing of APP |
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| Authors: | Huttunen Henri J Greco Christopher Kovacs Dora M |
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| Affiliation: | Neurobiology of Disease Laboratory, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, United States. Henri_Huttunen@hms.harvard.edu |
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| Abstract: | Previous studies have shown that acyl-coenzyme A:cholesterol acyl transferase (ACAT), an enzyme that controls cellular equilibrium between free cholesterol and cholesteryl esters, modulates proteolytic processing of APP in cell-based and animal models of Alzheimer's disease. Here we report that ACAT-1 RNAi reduced cellular ACAT-1 protein by approximately 50% and cholesteryl ester levels by 22% while causing a slight increase in the free cholesterol content of ER membranes. This correlated with reduced proteolytic processing of APP and 40% decrease in Abeta secretion. These data show that even a modest decrease in ACAT activity can have robust suppressive effects on Abeta generation. |
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| Keywords: | RNAi Cholesterol Cholesteryl esters Amyloid-β Alzheimer’s disease Amyloid precursor protein ACAT |
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