Reticulon-4 receptor (RTN4R)

Reticulon-4 receptor (RTN4R), also widely known as Nogo-66 receptor (NgR), is a central nervous system cell surface receptor best known for mediating the inhibitory effects of myelin-derived proteins, including reticulon-4 (Nogo-A), oligodendrocyte myelin glycoprotein, and myelin-associated glycoprotein[3][7][9]. RTN4R is a glycosylphosphatidylinositol (GPI)-anchored protein containing leucine-rich repeats, expressed on neurons, where it restricts axonal growth and plasticity after development. RTN4R plays a major role in limiting axonal regeneration in the adult brain and spinal cord, making it an important focus for therapies aiming to promote recovery after CNS injuries such as spinal cord injury and stroke[3][6][9]. Drugs targeting this pathway (e.g., Cethrin) seek to counteract growth inhibition and promote neural repair, usually by interfering with downstream effectors such as the RhoA-ROCK pathway[3]. RTN4R is also studied in the context of neurodegenerative diseases, where excessive inhibition of plasticity or regeneration impairs recovery potential[3][6][7][9].

Other names

Nogo-66 receptorNogo receptor 1NgRRTN4R

Competitive inhibition of ligand binding (e.g., antagonists block RTN4R’s interaction with inhibitory myelin proteins to promote neurite outgrowth) - ROCK pathway inhibition downstream of RTN4R activation