It Takes More Than Two to Nogo

  title={It Takes More Than Two to Nogo},
  author={Clifford J. Woolf and Stefan Bloechlinger},
  pages={1132 - 1134}
Growth-inhibitory molecules present in the myelin sheath surrounding CNS neurons prevent the regeneration of injured nerve fibers. In a Perspective, [Woolf and Bloechlinger][1] discuss new findings published here [ (Liu et al .) ][2] and elsewhere revealing that three of these growth-inhibitory molecules all bind to the same receptor. This suggests that blocking this receptor may be a good therapeutic approach to promoting neuronal regeneration. [1]:… 

NgR acts as an inhibitor to axonal regeneration in adults.

One avenue for promotion of axonal regeneration is by virtue of blocking the inhibitory effects of NgR, which binds to the same neuronal glycosylphosphatidylinositol-anchored receptors (NgR) and transduce inhibitory signals to cells by the transmembrane co-receptor, p75.

No Nogo Now Where to Go?

Suppression of p75NTR Does Not Promote Regeneration of Injured Spinal Cord in Mice

It is shown that the depletion of the functional p75NTR did not promote the regeneration of the descending corticospinal tract and ascending sensory neurons in the spinal cord 2 weeks after spinal cord injury, and may not be a critical molecule mediating the function of myelin-associated inhibitory factors in vivo.

NgR RNA interference, combined with zymosan intravitreal injection, enhances optic nerve regeneration

It is concluded that endogenous NgR inhibition and exogenous trophic support both play independent, important roles in enhancing optic nerve axon regrowth and that the regenerative effect can be augmented when the two are combined.

Activity-induced and developmental downregulation of the Nogo receptor

Strong, rapid and transient downregulation of NgR mRNA in response to kainic acid and after wheel running in cortex and hippocampus suggests a role for NgR and Nogo-A in plasticity, learning and memory.

The Pivotal Role of RhoA GTPase in the Molecular Signaling of Axon Growth Inhibition after CNS Injury and Targeted Therapeutic Strategies

Several critical points of convergence within the developing or regenerating neuron for mediating intracellular cell signaling effects on the growth cone cytoskeleton have been identified, and their modulation has produced marked increases in axon outgrowth within the “nonpermissive” milieu of the adult injured CNS.



Myelin-Associated Glycoprotein as a Functional Ligand for the Nogo-66 Receptor

It is shown that MAG binds directly, with high affinity, to NgR, and Cleavage of GPI-linked proteins from axons protects growth cones from MAG-induced collapse, and dominant-negative NgR eliminates MAG inhibition of neurite outgrowth.

Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein

The IN-1 antibody, which recognizes NI35 and NI250(Nogo), allows moderate degrees of axonal regeneration and functional recovery after spinal cord injury, and provides a molecular basis to assess the contribution of Nogo to the failure ofAxonal regeneration in the adult CNS.

Nogo-66 receptor antagonist peptide promotes axonal regeneration

The Nogo-66(1–40) antagonist peptide (NEP1-40) blocks Nogo or CNS myelin inhibition of axonal outgrowth in vitro, demonstrating that NgR mediates a significant portion of axon outgrowth inhibition by myelin.

Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1

Cl cloning of nogo A, the rat complementary DNA encoding NI-220/250 is reported, showing that Nogo-A is a potent inhibitor of neurite growth and an IN-1 antigen produced by oligodendrocytes, and may allow the generation of new reagents to enhance CNS regeneration and plasticity.

Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration

It is shown that the extracellular domain of Nogo (Nogo-66) inhibits axonal extension, but does not alter non-neuronal cell morphology, and a multivalent form of the N terminus of Noga-A affects the morphology of both neurons and other cell types.

Inactivation of Rho Signaling Pathway Promotes CNS Axon Regeneration

It is reported that injured axons regrow directly on complex inhibitory substrates when Rho GTPase is inactivated, indicating that targeting signaling mechanisms converging to Rho stimulates axon regeneration on inhibitory CNS substrates.

Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth

It is shown that a glycosylphosphatidylinositol-anchored CNS myelin protein, oligodendrocyte-myelin glycoprotein (OMgp), is a potent inhibitor of neurite outgrowth in cultured neurons and that Interfering with the OMgp/NgR pathway may allow lesioned axons to regenerate after injury in vivo.

The p75 receptor transduces the signal from myelin-associated glycoprotein to Rho

It is shown that the neurotrophin receptor p75 (p75NTR) is the signal transducing element for myelin-associated glycoprotein (MAG), and Ganglioside GT1b, which is one of the binding partners of MAG, specifically associates with p75N TR, which may form a receptor complex for MAG to transmit the inhibitory signals in neurons.