G-protein coupled receptors involved in the resolution of inflammation: Ligands and therapeutic perspectives

Dysregulated inflammation is a central pathological process in diverse disease states, in-cluding neurodegenerative disorders. The recent concept of “resolution of inflammation” is offering a conceptual change for the diagnosis and the development of new therapeutic approaches for chronic inflammatory diseases. Resolution of inflammation terminates the inflammatory response promoting the return to tissue homeostasis through the action of several classes of mediators, termed specialized pro-resolving lipid mediators (SPMs), that include lipoxins, resolvins, protectins, and maresins. SPMs provide “stop signals” that reduce the number of immune cells at the site of insult and increase the clearance of apoptotic cells through phagocytosis. SPMs elicit their effects through the interaction with specific G-protein coupled receptors (GPCRs). The elucidation of the pathways downstream of the GPCRs involved in the resolution of chronic inflammation is opening novel opportunities to generate novel anti-inflammatory agents. This review focuses on the SPMs and the receptors through which their effects are mediated. The medicinal chemistry of the modulators of the GPCRs involved in the resolution of inflammation will be illustrated, by highlighting the potential for developing new anti-inflammatory drugs.