NgR1

NgR1 (Nogo receptor 1, RTN4R) is a glycosylphosphatidylinositol-anchored neuronal receptor that mediates the inhibitory effects of several myelin-associated ligands, including Nogo-A, myelin-associated glycoprotein (MAG), and oligodendrocyte myelin glycoprotein (OMgp), thereby restricting axonal growth and structural plasticity in the adult central nervous system (CNS)^[1][2]. Mechanistically, because NgR1 lacks an intracellular signaling domain, it functions through a receptor complex containing co-receptors such as p75^NTR^ or TROY together with LINGO-1, which transduces downstream inhibitory signaling associated with growth cone collapse and axon regeneration failure^[2][3]. Consequently, NgR1 has become a central molecular target in studies of CNS injury, where blockade of NgR1 signaling promotes axonal regeneration and functional recovery in experimental spinal cord injury models^[4]. In disease-relevant contexts, NgR1 and its ligands are detected in demyelinating lesions, and Nogo-NgR1 signaling has been implicated in mechanisms that limit neurorepair and neural plasticity during chronic neuroinflammatory disorders such as multiple sclerosis^[5]. Compared with related family members, NgR1 displays broader ligand recognition, binding Nogo, MAG, and OMgp, whereas NgR2 preferentially binds MAG and exhibits distinct biological specificity, highlighting the unique role of NgR1 in myelin-associated growth inhibition^[2][6]. For experimental applications, the antagonist peptide NEP1-40 competitively inhibits NgR1 activation and remains a widely used tool for investigating axon regeneration and neural repair mechanisms in vivo and in vitro^[4].