RGD Reference Report - Inhibition of p75(NTR) in glia potentiates TrkA-mediated survival of injured retinal ganglion cells. - Rat Genome Database

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Inhibition of p75(NTR) in glia potentiates TrkA-mediated survival of injured retinal ganglion cells.

Authors: Lebrun-Julien, F  Morquette, B  Douillette, A  Saragovi, HU  Di Polo, A 
Citation: Lebrun-Julien F, etal., Mol Cell Neurosci. 2009 Apr;40(4):410-20. Epub 2008 Dec 25.
RGD ID: 5684376
Pubmed: PMID:19146958   (View Abstract at PubMed)
DOI: DOI:10.1016/j.mcn.2008.12.005   (Journal Full-text)

Little is known about the molecular mechanisms that limit the ability of retinal neurons to respond to neurotrophic factor stimulation following axonal injury. In the adult retina, nerve growth factor (NGF) binds to TrkA (expressed by neurons) and p75(NTR) (expressed by Muller glia), but fails to promote the survival of axotomized retinal ganglion cells (RGCs). We addressed the functional role of TrkA and p75(NTR) in this lack of survival by using peptidomimetic agonistic or antagonistic ligands specific for each receptor. While administration of exogenous NGF failed to rescue axotomized RGCs, administration of selective TrkA agonists led to robust neuroprotection. Surprisingly, we found a remarkable survival of axotomized RGCs following pharmacological inhibition of p75(NTR) or in p75(NTR) knockout mice. Combination of NGF or TrkA agonists with p75(NTR) antagonists further potentiated RGC neuroprotection in vivo, an effect that was greater than each treatment alone. NGF can therefore be neuroprotective when acting on neuronal TrkA receptors but engagement of p75(NTR) on glial cells antagonizes this effect. Our data reveal a novel mechanism by which p75(NTR) expressed on retinal glia can profoundly influence neuronal survival.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of neuron apoptotic process  IMP 5684376 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ntrk1  (neurotrophic receptor tyrosine kinase 1)


Additional Information