Formyl peptide receptor 2, as an important target for ligands triggering the inflammatory response regulation: a link to brain pathology

Formyl peptide receptors (FPRs) belong to the family of seven-transmembrane G protein-coupled receptors. Among them, FPR2 is a low affinity receptor for N-formyl peptides and is considered the most promiscuous member of FPRs. FPR2 is able to recognize a broad variety of endogenous or exogenous ligands, ranging from lipid to proteins and peptides, including non-formylated peptides. Due to this property FPR2 has the ability to modulate both pro- and anti-inflammatory response, depending on the nature of the bound agonist and on the different recognition sites of the receptor. Thus, FPR2 takes part not only in the proinflammatory response but also in the resolution of inflammation (RoI) processes. Recent data have indicated that the malfunction of RoI may be the background for some central nervous system (CNS) disorders. Therefore, much interest is focused on endogenous molecules called specialized pro-resolving mediators (SPMs), as well as on new synthetic FPR2 agonists, which kick-start the resolution of inflammation (RoI) and modulate its course. Here, we shed some light on the general characteristics of the FPR family in humans and in the experimental animals. Moreover, we present a guide to understanding the “double faced” action of FPR2 activation in the context of immune-related diseases of the CNS.