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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Available from: Nina F Schor, Sep 30, 2015
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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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    ABSTRACT: Due to its abundance, easy retrieval, and plasticity characteristics, adipose-tissue-derived stromal cells (ATSCs) present unquestionable advantages over other adult-tissue-derived stem cells. Based on the in silico analysis of our previous data reporting the ATSC-specific expression profiles, the present study attempted to clarify and validate at the functional level the expression of the neurospecific genes expressed by ATSC both in vitro and in vivo. This allowed evidencing that ATSCs express neuro-specific trophins, metabolic genes, and neuroprotective molecules. They were in fact able to induce neurite outgrowth in vitro, along with tissue-specific commitment along the neural lineage and the expression of the TRKA neurotrophin receptor in vivo. Our observation adds useful information to recent evidence proposing these cells as a suitable tool for cell-based applications in neuroregenerative medicine.
    BioMed Research International 12/2011; 2011:468705. DOI:10.1155/2011/468705 · 2.71 Impact Factor
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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. "
    Breakthroughs in Melanoma Research, 06/2011; , ISBN: 978-953-307-291-3
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    ABSTRACT: During spermatogenesis, spermatogonial stem cells, undifferentiated and differentiated spermatogonia, spermatocytes, spermatids and spermatozoa all express specific antigens, yet the functions of many of these antigens remain unexplored. Studies in the past three decades have shown that many of these transiently expressed genes in developing germ cells are proto-oncogenes and oncogenes, which are expressed only in the testis and various types of cancers in humans and rodents. As such, these antigens are designated cancer/testis antigens (CT antigens). Since the early 1980s, about 70 families of CT antigens have been identified with over 140 members are known to date. Due to their restricted expression in the testis and in various tumors in humans, they have been used as the target of immunotherapy. Multiple clinical trials at different phases are now being conducted with some promising results. Interestingly, in a significant number of cancer patients, antibodies against some of these CT antigens were detected in their sera. However, antibodies against these CT antigens in humans under normal physiological conditions have yet to be reported even though many of these antigens are residing outside of the blood-testis barrier (BTB), such as in the basal compartment of the seminiferous epithelium and in the stem cell niche in the testis. In this review, we summarize latest findings in the field regarding several selected CT antigens which may be intimately related to spermatogenesis due to their unusual restricted expression during different discrete events of spermatogenesis, such as cell cycle progression, meiosis and spermiogenesis. This information should be helpful to investigators in the field to study the roles of these oncogenes in spermatogenesis.
    07/2011; 1(3):209-220. DOI:10.4161/spmg.1.3.17990
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