CD36 gene polymorphisms and Alzheimer's disease
2020
Abstract Involvement of scavenger receptors in diseases such as atherosclerosis and cancer has been well known, but their role in the pathogenesis of neurodegenerative disorders is less well understood. Promotion of neurodegeneration in the brain has been suggested to take place via mechanisms comprising reactive oxygen species (ROS). Indeed, stimulation of production of inflammatory cytokines is associated with the progression of Alzheimer disease. This chapter focuses on the role of a class B scavenger receptor CD36 in the pathogenesis of Alzheimer disease. The major hypotheses of Alzheimer pathogenesis include, among others, the amyloid hypothesis, disturbances of cholesterol metabolism, central nervous system inflammatory processes, and oxidative stress. CD36 receptor is known to interfere with all these pathogenic processes. Furthermore, CD36 is involved in mechanisms of vascular growth, internalization of pathogens (bacteria, fungi), internalization of abeta protein, and gustatory perception of fatty acids as well as central processing of olfactory signals. CD36 receptor affects blood cholesterol levels, and, while CD36 receptor itself does not internalize abeta into microglia, it influences the phagocytosis by other scavenger receptors. At high abeta levels, the CD36 stimulates ROS production via nicotinamide adenine dinucleotide phosphate oxidase activation and secretion of IL-1β, IL-1α, and IL-18. We shall also discuss how inflammasome mediated pyroptosis could be important in the pathogenesis of Alzheimer disease. The final section of the chapter will discuss how specific polymorphisms or mutations of the CD36 receptor gene might influence the pathogenesis of Alzheimer disease. We conclude that it is necessary to consider not only the polymorphisms in exons but also polymorphisms in regulatory regions of the CD36 gene. Therefore, sequencing of the entire CD36 gene in Alzheimer disease patients should be performed, as this is the only way to identify all the polymorphisms and mutations in CD36 gene that could contribute to the mechanisms and/or risk of Alzheimer disease.
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