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The promiscuous low affinity neurotrophin co-receptor p75NTR, a member of the nerve tumor necrosis factor (TNF) receptor superfamily, mediates neuronal survival as well as death, and interacts with Trk receptors to increase their affinity for neurotrophins. Furthermore, p75NTR is the transmembrane signalling moiety which associates with the NOGO binding receptor for all CNC myelin-derived axon growth inhibitors in the injured CNS. We have shown in rats that intravitreal implan...

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ea0010p26 | Cytokines, growth factors, growth and development | SFE2005

Ahmed Z , Mazibrada G , Dent R , Berry M , Logan A

Upon binding of myelin-derived axon growth inhibitory ligands to the Nogo receptor (NgR), a complex is formed with LINGO-1 and the low affinity neurotrophin receptor p75NTR, which initiates axon growth cone collapse via a Rho-A-mediated pathway. We reasoned that, after tumor necrosis factor-α converting enzyme (TACE) cleavage of p75NTR, which triggers the initiation of regulated intramembrane proteolysis (RIP), signalling of growth cone collap...

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ea0008go2 | (1) | SFE2004

siRNA-Mediated Knock Down of NgR, p75NTR and Rho-A Disinhibits Neurotrophin-Induced Dorsal Root Ganglia Neurite Outgrowth on CNS Myelin

Ahmed Z , Dent RG , Suggate EL , Berry M , Logan A

Central nervous system neurones are generally incapable of regenerating their axons after injury due to the limited availability of neurotrophins, the development of a glial scar, and the presence of multiple axon growth inhibitors. We therefore designed short interfering RNA (siRNA) sequences to knock down components of the inhibitory signalling cascade and tested their ability to disinhibit the growth of FGF2-stimulated dorsal root ganglia neurone (DRGN) neurites in the pres...

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ea0019p210 | Neuroendocrinology and behaviour | SFEBES2009

EGFR antagonists promote disinhibited retinal ganglion cell axon regeneration by a glial-dependent mechanism

Morrison K , Ahmed Z , Leadbeater W , Gonzalez AM , Berry M , Logan A

It was reported that the inhibition of central nervous system (CNS) axon growth is mediated by Ca2+-dependent phosphorylation of epidermal growth factor receptor (pEGFR) and that local administration of small molecule EGFR antagonists to optic nerve lesions promoted retinal ganglion cell (RGC) axon regeneration (Koprivica et al. 2005). This result was attributed to suppression of EGFR kinase, which neutralised the axonal growth inhibitory potency of CNS myeli...

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Endocrine Abstracts

Receptor Shedding: A Novel Mechanism for the Disinhibition of CNS Neuronal Growth

siRNA-Mediated Knock Down of NgR, p75NTR and Rho-A Disinhibits Neurotrophin-Induced Dorsal Root Ganglia Neurite Outgrowth on CNS Myelin

EGFR antagonists promote disinhibited retinal ganglion cell axon regeneration by a glial-dependent mechanism

BiosciAbstracts