EGFR Activation Mediates Inhibition of Axon Regeneration by Myelin and Chondroitin Sulfate Proteoglycans

@article{Koprivica2005EGFRAM,
  title={EGFR Activation Mediates Inhibition of Axon Regeneration by Myelin and Chondroitin Sulfate Proteoglycans},
  author={Vuk Koprivica and Kin-Sang Cho and Jong Bae Park and Glenn Yiu and Jasvinder K. Atwal and Bryan B. Gore and Jieun A. Kim and Estelle Lin and Marc Tessier-Lavigne and Dong Feng Chen and Zhigang He},
  journal={Science},
  year={2005},
  volume={310},
  pages={106 - 110}
}
Inhibitory molecules associated with myelin and the glial scar limit axon regeneration in the adult central nervous system (CNS), but the underlying signaling mechanisms of regeneration inhibition are not fully understood. Here, we show that suppressing the kinase function of the epidermal growth factor receptor (EGFR) blocks the activities of both myelin inhibitors and chondroitin sulfate proteoglycans in inhibiting neurite outgrowth. In addition, regeneration inhibitors trigger the… 
View on AAAS
ncbi.nlm.nih.gov
341 Citations
Highly Influential Citations
25
Background Citations
128
Methods Citations
7
Results Citations
7

341 Citations

Citation Type

Citation Type

Repulsion of cerebellar granule neurons by chondroitin sulfate proteoglycans is mediated by MAPK pathway
Central Nervous System Regeneration Inhibitors and their Intracellular Substrates
TLDR
An overview of the molecules, receptors, and signaling pathways that inhibit CNS regeneration are presented, with a particular focus on the intracellular signaling machinery that may function as convergent targets for multiple inhibitory ligands.
The roles of neuronal and glial precursors in overcoming chondroitin sulfate proteoglycan inhibition
Epidermal growth factor receptor antagonists and CNS axon regeneration: Mechanisms and controversies
Advances in the Signaling Pathways Downstream of Glial-Scar Axon Growth Inhibitors
TLDR
This review will focus on recent advances in the downstream signaling pathways of scar-mediated inhibition and their potential as the molecular targets for CNS repair.
Proteoglycans in the central nervous system: plasticity, regeneration and their stimulation with chondroitinase ABC.
TLDR
The structures and properties of the different CSPGs in the normal and damaged CNS, the use of the enzyme chondroitinase ABC to promote neural regeneration and plasticity, and mechanisms of action and possible therapeutic uses of this enzyme are detailed.
Inhibiting Epidermal Growth Factor Receptor Improves Structural, Locomotor, Sensory, and Bladder Recovery from Experimental Spinal Cord Injury
TLDR
It is shown that rats subjected to weight-drop spinal cord injury can be effectively treated by direct delivery of a potent EGFR inhibitor to the injured area, leading to significantly better functional and structural outcome.
Neurotrophins support regenerative axon assembly over CSPGs by an ECM-integrin-independent mechanism
TLDR
By using regenerating adult dorsal root ganglion neurons, it is shown that chondroitin sulfate proteoglycans inhibit axon assembly by a different mechanism from myelin-based inhibitors, and that the GSK-3β-APC pathway, previously shown to mediate developing axon growth, is also necessary for axon regeneration.
Glial inhibition of CNS axon regeneration
TLDR
The molecular basis of inhibitory molecules in CNS myelin as well as proteoglycans associated with astroglial scarring are evaluated and their contributions to the limitation of long-distance axon repair and other types of structural plasticity are evaluated.
Receptor Tyrosine Kinases: Molecular Switches Regulating CNS Axon Regeneration
TLDR
The most relevant recent findings pertinent to different classes of the RTK family of molecules are highlighted and summarised, with a particular focus on elucidating their role in CNS axon regeneration.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 28 REFERENCES
The Nogo-66 receptor: focusing myelin inhibition of axon regeneration
Inactivation of Rho Signaling Pathway Promotes CNS Axon Regeneration
TLDR
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.
Myelin-associated inhibitors of axonal regeneration in the adult mammalian CNS
  • M. Filbin
  • Biology, Chemistry
    Nature Reviews Neuroscience
  • 2003
TLDR
Advances in the field have identified many new targets for therapeutic intervention to encourage nerve regeneration after spinal cord or brain injury.
The Nogo signaling pathway for regeneration block.
TLDR
Findings may ultimately allow for the development of strategies to alleviate the inhibitory effects of myelin-associated inhibitors in an effort to encourage axon regeneration after spinal cord and brain injury.
Myelin-Associated Glycoprotein Interacts with the Nogo66 Receptor to Inhibit Neurite Outgrowth
Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration
TLDR
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.
Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth
TLDR
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.
Regeneration beyond the glial scar
TLDR
Chondroitin and keratan sulphate proteoglycans are among the main inhibitory extracellular matrix molecules that are produced by reactive astrocytes in the glial scar, and they are believed to play a crucial part in regeneration failure.
A TNF Receptor Family Member, TROY, Is a Coreceptor with Nogo Receptor in Mediating the Inhibitory Activity of Myelin Inhibitors
TAJ/TROY, an Orphan TNF Receptor Family Member, Binds Nogo-66 Receptor 1 and Regulates Axonal Regeneration
...
1
2
3
...