Neuroprotectin D1 receptor (G protein-coupled receptor 37) (GPR37)

The Neuroprotectin D1 receptor, primarily identified as G protein-coupled receptor 37 (GPR37), is a key mediator of the pro-resolving and neuroprotective effects of Neuroprotectin D1 (NPD1), a docosahexaenoic acid (DHA)-derived lipid mediator [1, 16]. Activation of GPR37 by NPD1 triggers signaling pathways that inhibit pro-inflammatory cytokine production, promote macrophage phagocytosis (efferocytosis), and enhance neuronal survival under conditions of oxidative stress or ischemia [1, 3]. NPD1 also interacts with other targets, including G protein-coupled receptor 32 (GPR32) and the nuclear receptor PPAR-gamma, to modulate gene expression and amyloid processing [11, 15, 19]. The receptor plays a critical role in resolving neuroinflammation and is a potential therapeutic target for neurodegenerative diseases such as Alzheimer's and Parkinson's, as well as stroke and chronic pain [3, 4, 16]. Therapeutic strategies involve the use of stable NPD1 analogs or small-molecule agonists like artesunate to harness these protective pathways [1, 12]. However, a significant therapeutic challenge is the association of GPR37 misfolding and accumulation with endoplasmic reticulum stress and dopaminergic neuron loss in Parkinson's disease [1, 5]. Research also indicates that NPD1 signaling through its receptors can limit the progression of retinal degeneration and promote vascular repair in retinopathy [8, 13]. Overall, the Neuroprotectin D1 receptor system represents a vital endogenous mechanism for maintaining nervous system homeostasis and resolving inflammatory damage [3, 12].

Other names

G protein-coupled receptor 37PAELRParkin-associated endothelin-like receptorEndothelin B receptor-like protein 1NPD1 receptorProtectin D1 receptor

Agonism of GPR37 and GPR32 receptors to activate pro-resolving and neuroprotective signaling pathways [1, 15, 19].