G protein-coupled receptor 37 (GPR37) (GPR37)

The G protein-coupled receptor 37 (GPR37), also known as the Protectin D1 receptor, is a high-affinity, stereoselective binding site for the docosahexaenoic acid-derived specialized pro-resolving mediator (SPM) Neuroprotectin D1 (NPD1/PD1) [Marcheselli et al., 2003; Bang et al., 2018]. It is important to distinguish this lipid mediator receptor from the Programmed Cell Death 1 (PD-1) immune checkpoint protein. This receptor is expressed on human neutrophils and macrophages, where it serves as a critical regulator of the resolution phase of inflammation [Serhan et al., 2006]. Activation of the receptor by NPD1/PD1 triggers signaling pathways that significantly reduce neutrophil transmigration and chemotaxis, effectively limiting the inflammatory influx to the site of injury [Duffield et al., 2006]. Simultaneously, it enhances the phagocytic clearance of apoptotic cells and debris by macrophages, a process known as efferocytosis, which is essential for tissue homeostasis [Bang et al., 2018]. In various disease contexts, the NPD1-GPR37 axis is vital for protecting tissues such as the retina, brain, and lungs from excessive inflammatory damage and oxidative stress [Serhan, 2014]. Dysregulation of this signaling pathway is associated with chronic inflammatory conditions, neurodegenerative diseases like Parkinson's, and impaired wound healing [Marcheselli et al., 2003]. Therapeutic strategies targeting this receptor involve the development of stable synthetic analogs of NPD1 or small-molecule GPR37 agonists to promote resolution without the side effects of traditional immunosuppressants [Levy et al., 2007].

Other names

Protectin D1 receptorNeuroprotectin D1 receptorNPD1 receptorPAELRParkin-associated endothelin receptor-like receptorPD1R

Agonist binding to the receptor triggers pro-resolving signaling pathways that inhibit neutrophil chemotaxis and promote macrophage-mediated efferocytosis of apoptotic cells.