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Morales-Lazaro, Sara L; Rosenbaum, Tamara (2019)


Adv. Exp. Med. Biol. 1135():105-117
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Cholesterol is the one of the major constituents of cell membranes providing these structures with a certain degree of rigidity. Proteins, such as ion channels, are molecules inserted in cell membranes and their activity is regulated by cholesterol and other molecules of a lipidic nature present in them. The molecular mechanisms underlying the regulation of ion channels by lipids and similar molecules have been an object of study for several years. A little over two decades ago, the first mammalian member of the Transient Receptor Potential (TRP) family of ion channels was cloned. This protein, the TRPV1 channel, was shown to integrate several types of noxious signals in sensory neurons and to participate in processes associated to the generation of pain. Thus, TRPV1 has become the target of intense research directed towards finding potential inhibitors of its activity in an effort to control pain. To date, several activators and positive modulators of the activity of TRPV1 have been described. However, very few naturally-occurring inhibitors are known. An endogenously-produced molecule that inhibits the activity of TRPV1 is cholesterol. This chapter focuses on describing the mechanisms by which the activity of TRPV1 can be regulated by this sterol.