RGD Reference Report - A novel p75NTR signaling pathway promotes survival, not death, of immunopurified neocortical subplate neurons. - Rat Genome Database

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A novel p75NTR signaling pathway promotes survival, not death, of immunopurified neocortical subplate neurons.

Authors: DeFreitas, MF  McQuillen, PS  Shatz, CJ 
Citation: DeFreitas MF, etal., J Neurosci. 2001 Jul 15;21(14):5121-9.
RGD ID: 5508783
Pubmed: PMID:11438587   (View Abstract at PubMed)
PMCID: PMC6762833   (View Article at PubMed Central)

Subplate neurons of mammalian neocortex undergo pronounced cell death postnatally, long after they have matured and become incorporated into functional cortical circuits. They express the p75 neurotrophin receptor (p75NTR), which is known to signal cell death in some types of neurons via the activation of sphingomyelinase and the concomitant increase in the sphingolipid ceramide. To evaluate the role of p75NTR in subplate neurons, they were immunopurified and cultured in vitro. Contrary to its known function as a death receptor, ligand binding to p75NTR promotes subplate neuron survival. Moreover, p75NTR-dependent survival is blocked by inhibition of ceramide synthesis and rescued by addition of its precursor sphingomyelin. Inhibition of Trk signaling does not block survival, nor is Trk signaling alone sufficient to promote survival. Thus, ligand-dependent p75NTR regulation of the ceramide pathway mediates survival in certain neurons and may represent an important target for neuroprotective drugs in degenerative diseases involving p75NTR-expressing neurons, such as Alzheimer's disease.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of neuron apoptotic process  IMP 5508783neocortical subplate neurons and via ceramideRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ngfr  (nerve growth factor receptor)


Additional Information