Nogo-66 receptor antagonist peptide promotes axonal regeneration

  title={Nogo-66 receptor antagonist peptide promotes axonal regeneration},
  author={Tadzia Grandpr{\'e} and Shuxin Li and Stephen M. Strittmatter},
Myelin-derived axon outgrowth inhibitors, such as Nogo, may account for the lack of axonal regeneration in the central nervous system (CNS) after trauma in adult mammals. A 66-residue domain of Nogo (Nogo-66) is expressed on the surface of oligodendrocytes and can inhibit axonal outgrowth through an axonal Nogo-66 receptor (NgR). The IN-1 monoclonal antibody recognizes Nogo-A and promotes corticospinal tract regeneration and locomotor recovery; however, the undefined nature of the IN-1 epitope… 

Genetic deletion of the Nogo receptor does not reduce neurite inhibition in vitro or promote corticospinal tract regeneration in vivo.

NgR is not essential for mediating inhibitory signals from CNS myelin, at least in the neurons tested, whereas p75(NTR) plays a central role in this response.

Delayed Systemic Nogo-66 Receptor Antagonist Promotes Recovery from Spinal Cord Injury

Subcutaneous treatment with the NgR antagonist peptide NEP1–40 (Nogo extracellular peptide, residues 1–40) results in extensive growth of corticospinal axons, sprouting of serotonergic fibers, upregulation of axonal growth protein SPRR1A (small proline-rich repeat protein 1A), and synapse re-formation, andLocomotor recovery after thoracic spinal cord injury is enhanced.

Soluble Nogo Receptor Down-regulates Expression of Neuronal Nogo-A to Enhance Axonal Regeneration*

The results indicate that neuronal Nogo-A is an important intermediate in neurite growth dynamics and its expression is regulated by signals related to axonal injury and regeneration, that CNS myelin appears to activate signaling events that mimicAxonal injury, and that NgSR released from QHNgSR may be used to improve recovery after injury.

The Nogo receptor, its ligands and axonal regeneration in the spinal cord; A review

It is not clear whether antibodies against Nogo act on oligodendrocytes/myelin or by binding to neuronal Nogo, or whether they can stimulate regeneration of ascending axons in the spinal cord, most of which express little or no NgR.

Nogo-C is sufficient to delay nerve regeneration

Inhibition of Retinal Ganglion Cell Axonal Outgrowth Through the Amino-Nogo-A Signaling Pathway

The results suggest that Amino-Nogo inhibits RGC axonal outgrowth primarily through the integrin αv signaling pathway.



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.

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-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.

Recovery from spinal cord injury mediated by antibodies to neurite growth inhibitors

It is reported here that brain stem–spinal as well as corticospinal axons undergo regeneration and anatomical plasticity after application of IN-1 antibodies, and there is a recovery of specific reflex and locomotor functions after spinal cord injury in these adult rats.

Neurobiology: Inhibitor of neurite outgrowth in humans

This work has used this bovine sequence to identify the human Nogo gene and has isolated complementary DNA clones encoding three different Nogo isoforms that are potent inhibitors of neurite outgrowth and which may help block the regeneration of the central nervous system in adults.

Bovine CNS Myelin Contains Neurite Growth-Inhibitory Activity Associated with Chondroitin Sulfate Proteoglycans

The results strongly suggest that brevican and versican V2 are additional components of CNS myelin that contribute to its nonpermissive substrate properties for axonal growth.

Locomotor Recovery in Spinal Cord-Injured Rats Treated with an Antibody Neutralizing the Myelin-Associated Neurite Growth Inhibitor Nogo-A

Improved functional recovery in the mAb IN-1-treated rats suggest that the increased plastic and regenerative capabilities of the CNS after Nogo-A neutralization result in a functionally meaningful rewiring of the motor systems.

Neuronal and Non-Neuronal Collapsin-1 Binding Sites in Developing Chick Are Distinct from Other Semaphorin Binding Sites

The staining patterns for mouse semaphorin D/III and chick collapsin-1 fusion proteins are indistinguishable from one another but quite separate from that for semaphorein B and M-semaphor in F fusion proteins, which imply that a family of high-affinity semphorin binding sites similar in complexity to the semaphorbin ligand family exists.