Reticulon-4 (Nogo-A isoform) (Nogo-A)

Reticulon-4, specifically the Nogo-A isoform, is a potent myelin-associated inhibitor of axonal regeneration in the adult central nervous system (CNS). It is primarily expressed by oligodendrocytes and localized to the innermost and outermost loops of the myelin sheath, where it serves as a physical and biochemical barrier to nerve repair after injury. Nogo-A exerts its inhibitory effects by binding to the Nogo receptor (NgR1) and the sphingosine-1-phosphate receptor 2 (S1PR2), triggering intracellular signaling cascades that lead to growth cone collapse and the stabilization of the actin cytoskeleton. In pathological conditions such as spinal cord injury, stroke, and multiple sclerosis, the presence of Nogo-A prevents the spontaneous recovery of damaged neural circuits. Therapeutic strategies targeting Nogo-A, including monoclonal antibodies like Ozanezumab and decoy receptors, aim to neutralize this inhibition to promote functional recovery and neuroplasticity. Clinical trials have explored these interventions to enhance motor function in patients with chronic neurological deficits.

Other names

RTN4Nogo proteinNeurite outgrowth inhibitorNeuroendocrine-specific proteinNSPASYRTN-X

Monoclonal antibodies or decoy receptors bind to and neutralize Nogo-A, preventing it from interacting with the Nogo receptor (NgR1) complex, thereby lifting the inhibition on axonal regrowth and promoting neuroregeneration.