Targeting the Nogo Receptor to Treat Central Nervous System Injuries

Axonal damage is a key pathology in many injuries of the central nervous system (CNS), such as spinal cord injury, traumatic brain injury and stroke, as well as in multiple sclerosis. An attractive drug discovery strategy to treat such conditions is to search for agents that promote CNS axonal regeneration. Historically, limited knowledge concerning the basis of poor CNS regeneration has precluded a rational drug discovery approach for promoting axonal regeneration. The recent identification of the Nogo receptor, which interacts with inhibitory myelin protein, established the crucial role of this molecular pathway in mediating the inhibitory effects of CNS myelin. This provides an unprecedented opportunity to manipulate adult CNS axonal regeneration. The development of therapeutics targeting the Nogo receptor has the potential to promote functional recovery and reverse the devastating consequences of CNS injuries.

[1]  Santiago Ramón y Cajal,et al.  Degeneration & regeneration of the nervous system , 1928 .

[2]  D. D.-B.,et al.  Degeneration and Regeneration of the Nervous System , 1930, Nature.

[3]  A. Scheibel,et al.  Degeneration and regeneration of the nervous system , 1960 .

[4]  F. Reiss.  A REPORT ON THE CONGRESS , 1964 .

[5]  P. Caroni,et al.  Antibody against myelin associated inhibitor of neurite growth neutralizes nonpermissive substrate properties of CNS white matter , 1988, Neuron.

[6]  M. Schwab,et al.  Two membrane protein fractions from rat central myelin with inhibitory properties for neurite growth and fibroblast spreading , 1988, The Journal of cell biology.

[7]  D. Mikol,et al.  A phosphatidylinositol-linked peanut agglutinin-binding glycoprotein in central nervous system myelin and on oligodendrocytes , 1988, The Journal of cell biology.

[8]  M. L. Le Beau,et al.  Structure and chromosomal localization of the gene for the oligodendrocyte-myelin glycoprotein , 1990, The Journal of cell biology.

[9]  M. Filbin,et al.  A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration , 1994, Neuron.

[10]  Yves-Alain Barde,et al.  Neurotrophin-3 enhances sprouting of corticospinal tract during development and after adult spinal cord lesion , 1994, Nature.

[11]  L. Mckerracher,et al.  Identification of myelin-associated glycoprotein as a major myelin-derived inhibitor of neurite growth , 1994, Neuron.

[12]  M. Schwab,et al.  Recovery from spinal cord injury mediated by antibodies to neurite growth inhibitors , 1995, Nature.

[13]  D. Basso,et al.  A sensitive and reliable locomotor rating scale for open field testing in rats. , 1995, Journal of neurotrauma.

[14]  F. Gage,et al.  Cellular Delivery of Neurotrophin-3 Promotes Corticospinal Axonal Growth and Partial Functional Recovery after Spinal Cord Injury , 1997, The Journal of Neuroscience.

[15]  S. Strittmatter,et al.  Rac1 Mediates Collapsin-1-Induced Growth Cone Collapse , 1997, The Journal of Neuroscience.

[16]  Douglas L. Kruse,et al.  Spinal Cord Injury: An Analysis of Medical and Social Costs , 1998 .

[17]  T. Yamashita,et al.  Neurotrophin Binding to the p75 Receptor Modulates Rho Activity and Axonal Outgrowth , 1999, Neuron.

[18]  G. Burnstock,et al.  The Effects of FK506 on Dorsal Column Axons Following Spinal Cord Injury in Adult Rats: Neuroprotection and Local Regeneration , 1999, Experimental Neurology.

[19]  Mark A. Banks,et al.  Spinal Cord Injury: An Analysis of Medical and Social Costs , 1999 .

[20]  J. Madsen,et al.  Inosine stimulates extensive axon collateral growth in the rat corticospinal tract after injury. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[21]  N. Leclerc,et al.  Inactivation of Rho Signaling Pathway Promotes CNS Axon Regeneration , 1999, The Journal of Neuroscience.

[22]  R. Prinjha,et al.  Neurobiology: Inhibitor of neurite outgrowth in humans , 2000, Nature.

[23]  Martin E. Schwab,et al.  Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1 , 2000, Nature.

[24]  M. Schwab,et al.  Regeneration of Lesioned Corticospinal Tract Fibers in the Adult Rat Induced by a Recombinant, Humanized IN-1 Antibody Fragment , 2000, The Journal of Neuroscience.

[25]  M. Schwab,et al.  Nogo-A, a Potent Inhibitor of Neurite Outgrowth and Regeneration , 2000, Biological chemistry.

[26]  Fumio Nakamura,et al.  Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein , 2000, Nature.

[27]  B. Trapp,et al.  Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions , 2001, Annals of neurology.

[28]  A. Fournier,et al.  Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration , 2001, Nature.

[29]  V. Dietz,et al.  Locomotor Recovery in Spinal Cord-Injured Rats Treated with an Antibody Neutralizing the Myelin-Associated Neurite Growth Inhibitor Nogo-A , 2001, The Journal of Neuroscience.

[30]  R. Segal,et al.  p75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp , 2002, Nature.

[31]  Zhigang He,et al.  Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth , 2002, Nature.

[32]  A. Fournier,et al.  Myelin-Associated Glycoprotein as a Functional Ligand for the Nogo-66 Receptor , 2002, Science.

[33]  M. Schwab,et al.  Functional recovery and neuroanatomical plasticity following middle cerebral artery occlusion and IN‐1 antibody treatment in the adult rat , 2002, Annals of neurology.

[34]  S. Strittmatter,et al.  Localization of Nogo-A and Nogo-66 Receptor Proteins at Sites of Axon–Myelin and Synaptic Contact , 2002, The Journal of Neuroscience.

[35]  James W. Fawcett,et al.  Chondroitinase ABC promotes functional recovery after spinal cord injury , 2002, Nature.

[36]  B. Ellezam,et al.  Rho Signaling Pathway Targeted to Promote Spinal Cord Repair , 2002, The Journal of Neuroscience.

[37]  P. Thibault,et al.  Oligodendrocyte‐myelin glycoprotein (OMgp) is an inhibitor of neurite outgrowth , 2002, Journal of neurochemistry.

[38]  E. Shooter,et al.  The Neurotrophin Receptor p75NTR as a Positive Modulator of Myelination , 2002, Science.

[39]  A. Fournier,et al.  Truncated Soluble Nogo Receptor Binds Nogo-66 and Blocks Inhibition of Axon Growth by Myelin , 2002, The Journal of Neuroscience.

[40]  Haining Dai,et al.  Spinal Axon Regeneration Induced by Elevation of Cyclic AMP , 2002, Neuron.

[41]  Marco Domeniconi,et al.  Myelin-Associated Glycoprotein Interacts with the Nogo66 Receptor to Inhibit Neurite Outgrowth , 2002, Neuron.

[42]  T. Yamashita,et al.  The p75 receptor transduces the signal from myelin-associated glycoprotein to Rho , 2002, The Journal of cell biology.

[43]  R. Coffin,et al.  Nogo Receptor mRNA Expression in Intact and Regenerating CNS Neurons , 2002, Molecular and Cellular Neuroscience.

[44]  M. Poo,et al.  A p75NTR and Nogo receptor complex mediates repulsive signaling by myelin-associated glycoprotein , 2002, Nature Neuroscience.

[45]  S. Strittmatter,et al.  Nogo-66 receptor antagonist peptide promotes axonal regeneration , 2002, Nature.

[46]  C. Bandtlow,et al.  Nogo-A and Myelin-Associated Glycoprotein Mediate Neurite Growth Inhibition by Antagonistic Regulation of RhoA and Rac1 , 2002, The Journal of Neuroscience.

[47]  M. Schwab,et al.  An engineered IN-1 F(ab) fragment with improved affinity for the Nogo-A axonal growth inhibitor permits immunochemical detection and shows enhanced neutralizing activity. , 2002, Protein engineering.

[48]  Yves-Alain Barde,et al.  The neurotrophin receptor p75(NTR): novel functions and implications for diseases of the nervous system. , 2002, Nature neuroscience.

[49]  J. Kim,et al.  ProNGF Induces p75-Mediated Death of Oligodendrocytes following Spinal Cord Injury , 2002, Neuron.

[50]  L. Olson.  Medicine: Clearing a path for nerve growth , 2002, Nature.

[51]  J. Schwab,et al.  The Rho/ROCK pathway mediates neurite growth-inhibitory activity associated with the chondroitin sulfate proteoglycans of the CNS glial scar , 2003, Molecular and Cellular Neuroscience.

[52]  T. Yamashita,et al.  The p75 receptor acts as a displacement factor that releases Rho from Rho-GDI , 2003, Nature Neuroscience.

[53]  G. McDermott,et al.  Structure of the Nogo Receptor Ectodomain A Recognition Module Implicated in Myelin Inhibition , 2003, Neuron.

[54]  M. Schwab,et al.  Anti—Nogo-A Antibody Infusion 24 Hours after Experimental Stroke Improved Behavioral Outcome and Corticospinal Plasticity in Normotensive and Spontaneously Hypertensive Rats , 2003, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[55]  B. Sommer,et al.  Characterization of two novel proteins, NgRH1 and NgRH2, structurally and biochemically homologous to the Nogo‐66 receptor , 2003, Journal of neurochemistry.

[56]  S. Strittmatter,et al.  Delayed Systemic Nogo-66 Receptor Antagonist Promotes Recovery from Spinal Cord Injury , 2003, The Journal of Neuroscience.

[57]  S. Strittmatter,et al.  The Nogo-66 receptor: focusing myelin inhibition of axon regeneration , 2003, Trends in Neurosciences.

[58]  M. Schwab,et al.  Functional Reorganization of the Motor Cortex in Adult Rats after Cortical Lesion and Treatment with Monoclonal Antibody IN-1 , 2003, The Journal of Neuroscience.

[59]  M. Filbin,et al.  Myelin-associated inhibitors of axonal regeneration in the adult mammalian CNS , 2003, Nature Reviews Neuroscience.

[60]  A. B. Huber,et al.  Nogo-A Inhibits Neurite Outgrowth and Cell Spreading with Three Discrete Regions , 2003, The Journal of Neuroscience.

[61]  M. Filbin.  Myelin-associated inhibitors of axonal regeneration in the adult mammalian CNS , 2003, Nature Reviews Neuroscience.

[62]  J. Saver,et al.  Annual Incidence of First Silent Stroke in the United States: A Preliminary Estimate , 2003, Cerebrovascular Diseases.

[63]  A. Fournier,et al.  Structure and axon outgrowth inhibitor binding of the Nogo‐66 receptor and related proteins , 2003, The EMBO journal.

[64]  A. Harvey,et al.  Intraocular elevation of cyclic AMP potentiates ciliary neurotrophic factor-induced regeneration of adult rat retinal ganglion cell axons , 2003, Molecular and Cellular Neuroscience.

[65]  A. Fournier,et al.  Rho Kinase Inhibition Enhances Axonal Regeneration in the Injured CNS , 2003, The Journal of Neuroscience.