期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
卷 1801, 期 8, 页码 960-965出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbalip.2010.04.003
关键词
Alzheimer's disease; A beta; ACAT; Cholesterol; Cholesteryl ester; Lipid droplet
资金
- Cure Alzheimer's Fund
- U.S. National Institutes of Health [R01 NS45860]
Alzheimer's disease (AD) is a devastating neurodegenerative disorder. Accumulation and deposition of the beta-amyloid (A beta) peptide generated from its larger amyloid precursor protein (APP) is one of the pathophysiological hallmarks of AD. Intracellular cholesterol was shown to regulate A beta production. Recent genetic and biochemical studies indicate that not only the amount, but also the distribution of intracellular cholesterol is critical to regulate A beta generation. Acyl-coenzyme A: cholesterol acyl-transferase (ACAT) is a family of enzymes that regulates the cellular distribution of cholesterol by converting membrane cholesterol into hydrophobic cholesteryl esters for cholesterol storage and transport. Using pharmacological inhibitors and transgenic animal models, we and others have identified ACAT1 as a potential therapeutic target to lower A beta generation and accumulation. Here we discuss data focusing on ACAT inhibition as an effective strategy for the prevention and treatment of AD. (C) 2010 Elsevier B.V. All rights reserved.
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