NogoA–Nogo receptor–Rho-associated protein kinase signaling pathway (NogoA–NgR–Rho–ROCK signaling pathway)

The NogoA–Nogo receptor–Rho-associated protein kinase (ROCK) signaling pathway is a key inhibitory pathway in the central nervous system (CNS) that restricts neurite outgrowth and axonal regeneration following injury. NogoA, a myelin-derived membrane protein, binds to the Nogo receptor (NgR) on neurons, which also requires co-receptors such as p75NTR and LINGO-1. This receptor complex activates the small GTPase RhoA and its effector kinase ROCK, leading to cytoskeletal rearrangements, growth cone collapse, and inhibition of axon extension. This pathway is important in development but becomes maladaptive after injury or in neurodegenerative conditions by preventing axonal regrowth and repair. Components of this pathway are being pursued as therapeutic targets in a range of neurodegenerative, neuroinflammatory, and neurotrauma conditions, and several ROCK inhibitors show promise in preclinical and clinical studies.

Other names

NogoA–NgR pathwayNogoA–RhoA/ROCK signalingNogo–NgR/Rho/ROCK pathwayMyelin-associated inhibitor pathway

Inhibition of RhoA/ROCK signaling to promote axonal outgrowth and regeneration or blockade of NogoA or NgR interactions to relieve axon growth inhibition.