Therapeutic potential of lipase inhibitor orlistat in Alzheimer's disease.
Emerging evidences indicate that elevated cholesterol and triglyceride levels precede Alzheimer's disease (AD) pathology. High caloric intake based on saturated fat raises hyperlipidaemia and also promotes AD pathology. As a result, strategy that limits the absorption of dietary fat and attenuates hyperlipidemia could be a useful medication for protective treatment of AD. As an active site-directed inhibitor of digestive lipases, orlistat effectively reduces dietary fat absorption and decreases total cholesterol and triglyceride levels in plasma. Orlistat also potently inhibits lipoprotein lipase, monoacylglycerol lipase and diacylglycerol lipase, which are also involved in AD causation. Taken together, orlistat inhibits lipases activities, thereby reduces dietary fat intake and ameliorates hyperlipidemia, which indicates a therapeutic potential of orlistat in protecting against AD pathology.
Du
Jing
J
Protein Science Key Laboratory of the Ministry of Education, Department of Biological Sciences and Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, PR China.
Wang
Zhao
Z
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007783:Lactones / Q000627:therapeutic use*; D008049:Lipase / Q000037:antagonists & inhibitors*; D008962:Models, Theoretical; D000077403:Orlistat
D004791:Enzyme Inhibitors; D007783:Lactones; D000077403:Orlistat; D008049:Lipase