CD36 is a member of the scavenger receptor family of pattern recognition receptors that are believed to have evolved with the innate immune system. CD36 binds a broad variety of ligands, including oxidized low density lipoprotein, thrombospondin- 1, malarial peptides, and apoptotic cells. Through binding of these ligands, CD36 is involved in such diverse processes as atherogenesis, angiogenesis, malarial pathogenesis, and tissue homeostasis. Despite its identification more than a decade ago, the physiological events regulated by CD36 ligation remain largely unknown. There is growing evidence to suggest that CD36 initiates cellular signaling, however the mechanism of this initiation, and the signal transduction pathways induced, are largely undefined. We now have evidence that beta-amyloid, a peptide central to the pathogenesis of Alzheimer's Disease, binds to CD36 and initiates activation of pro-inflammatory kinase pathways. Thus, Alzheimer's Disease might be added to the growing list of diseases whose pathogenesis may be modulated by CD36 signaling. Given its importance in two of the primary diseases associated with aging, atherogenesis and Alzheimer's Disease, understanding the mechanism of CD36 signaling is important. We propose to: (a) delineate the macrophage/microglial signaling cascade initiated by ligand binding of CD36, (b) identify the structural components of CD36 responsible for this signaling and (c) determine how CD36 signaling alters gene expression. These experiments will contribute to our understanding of how CD36 functions, and may provide important insights into its contribution to atherogenesis and Alzheimer's disease. A long term goal of these aims is to identify ways in which CD36 signaling might be abrogated, which may facilitate the identification of therapeutics designed to interrupt inflammatory signaling by CD36.
| Moore, Kathryn J; Goldberg, Ira J (2016) Emerging Roles of PCSK9: More Than a One-Trick Pony. Arterioscler Thromb Vasc Biol 36:211-2 |
| Moore, Kathryn J; Sheedy, Frederick J; Fisher, Edward A (2013) Macrophages in atherosclerosis: a dynamic balance. Nat Rev Immunol 13:709-21 |
| Sokolovska, Anna; Becker, Christine E; Ip, W K Eddie et al. (2013) Activation of caspase-1 by the NLRP3 inflammasome regulates the NADPH oxidase NOX2 to control phagosome function. Nat Immunol 14:543-53 |
| Pagler, Tamara A; Wang, Mi; Mondal, Mousumi et al. (2011) Deletion of ABCA1 and ABCG1 impairs macrophage migration because of increased Rac1 signaling. Circ Res 108:194-200 |
| Fernández-Hernando, Carlos; Suárez, Yajaira; Rayner, Katey J et al. (2011) MicroRNAs in lipid metabolism. Curr Opin Lipidol 22:86-92 |
| Wilkinson, Kim; Boyd, Justin D; Glicksman, Marcie et al. (2011) A high content drug screen identifies ursolic acid as an inhibitor of amyloid beta protein interactions with its receptor CD36. J Biol Chem 286:34914-22 |
| Rayner, Katey J; Sheedy, Frederick J; Esau, Christine C et al. (2011) Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis. J Clin Invest 121:2921-31 |
| Davalos, Alberto; Goedeke, Leigh; Smibert, Peter et al. (2011) miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling. Proc Natl Acad Sci U S A 108:9232-7 |
| Owens 3rd, A Phillip; Rateri, Debra L; Howatt, Deborah A et al. (2011) MyD88 deficiency attenuates angiotensin II-induced abdominal aortic aneurysm formation independent of signaling through Toll-like receptors 2 and 4. Arterioscler Thromb Vasc Biol 31:2813-9 |
| Higashimori, Mie; Tatro, Jeffrey B; Moore, Kathryn J et al. (2011) Role of toll-like receptor 4 in intimal foam cell accumulation in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 31:50-7 |
Showing the most recent 10 out of 31 publications
