Necdin and Neurotrophin Receptors: Interactors of Relevance for Neuronal Resistance to Oxidant Stress

Department of Pediatrics, University of Rochester Medical Center, Rochester, New York 14642, USA.
Pediatric Research (Impact Factor: 2.31). 12/2010; 69(4):279-84. DOI: 10.1203/PDR.0b013e31820a5773
Source: PubMed


Necdin is a protein known to interact with the neurotrophin receptors, neurotrophic tyrosine kinase receptor type 1 (TrkA) and 75 kD low-affinity neurotrophin receptor (p75NTR). TrkA and p75NTR play roles in development and disease of the nervous system and chemoresistance of nervous system tumors. Necdin deletion is associated with Prader-Willi syndrome. The present studies demonstrate that the effects of necdin on the susceptibility of neuroblastoma cells to oxidant stress are dependent on the ratio of p75NTR to TrkA in the cell. In low p75NTR:TrkA ratio cells, necdin down-regulation decreases sensitivity to oxidant stress and expression of and signaling through TrkA. In high p75NTR:TrkA cells, necdin down-regulation is without effect. The effects of necdin deletion on the developing nervous system may depend on the relative expression of p75NTR and TrkA in the cells of particular regions of the nervous system.

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    • "Our data could also suggest that ATSCs neurotrophic function resides in a sort of astrocyte-like phenotype, as they specifically express genes belonging to the glial phenotype, including VLDR, FGF2, and NDN, according to GOA annotations. To this end, the necdin homolog (NDN) gene, involved in the NGFB signalling pathway, is particularly relevant, as it drives glial migration during nervous system development and is expressed in the cell projections [23]. Although the neural transdifferentiation capacity of MSCs has been largely debated, many recent studies emphasise the possibility of both bone marrow- and adipose tissue derived-undifferentiated stromal cells to differentiate along the neuroectodermal lineage to neuronal-like cells of the ectodermal lineage, mainly in vitro [32–42]. "
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    • "Moreover, p75NTR induces apoptosis in the presence of NGF (Bunone et al., 1997), but this apoptotic signaling is inhibited by the presence of TrkA receptors (Eggert et al., 2000). Recently, it has been demonstrated that the effects of necdin, a protein known to interact with NTs receptors, on the susceptibility of NB cells to oxidant stress depend on the p75NTR/TrkA ratio in the cell (Ingraham et al., 2011). Although melanoma is a tumor derived from the neural crest, and shares with cancers of the same origin embryogenic and oncogenic pathways as well as common transcription factors (Wang et al., 2008; Gershon et al., 2005), it has been given less attention, as far as the role of NT. "

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