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Gene Review

NT3  -  3'-nucleotidase

Homo sapiens

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Disease relevance of NT3

  • Immunohistochemically, 34 of 47 pancreatic cancers (72 per cent) were mildly to markedly immunoreactive for NT-3 in the cytoplasma [1].
  • These data indicate that the accumulation of a 3'-nucleotidase substrate, such as PAP, mediates the toxicity of lithium [2].
  • The Leishmania donovani- inducible A2 gene regulatory system was used to differentially express in amastigotes two potential suicide genes: a truncated version of the L. donovani 3'-nucleotidase/nuclease expressed in the cytoplasm and the herpes simplex virus thymidine kinase gene [3].
  • Previously, we reported that over-expression of neurotrophin-3 (NT-3) promoted sprouting of axons in the injured but not uninjured spinal cord, suggesting that processes associated with the injury such as Wallerian degeneration (WD) participated to induce the neuroplasticity [4].

Psychiatry related information on NT3

  • Collectively, our data support a role for 3'-nucleotidase activity and PAP metabolism in aspects of lithium's mechanism of action and provide a platform for development of novel pharmacological modulators aimed at improving therapies for the treatment of bipolar disorder [2].

High impact information on NT3


Biological context of NT3

  • Additionally, we determined NT3 (neurotrophin 3) levels, a factor which exhibits neurotrophic properties at cholinergic neurons, and the concentration of which in these brain regions varies with CNTF genotype [7].
  • One included eight studies examining the association of schizophrenia with the A3 allele in a dinucleotide repeat polymorphism of the NT3 gene promoter (N=1938) [8].
  • We evaluated also the role of NGF, BDNF and NT3 in the modulation of cell migration and invasion and, finally, the effects of a pan Trk inhibitor, CEP-701 which has been included in some clinical trials for the treatment of PCa [9].
  • Conditional BDNF or NT-3 knockouts that are successful in selectively altering a vagal GI afferent pathway will be valuable for developing an understanding of that pathway's roles in GI function and food intake [10].
  • Thus, NT-3 promotes the conversion of neuroepithelial cells into neurons, whereas BDNF and NGF control the programmed cell death (apoptosis) that affects early postmitotic neuroblasts [11].

Anatomical context of NT3

  • Additionally, higher NT3 concentrations were found in this region, as well as in the frontal cortex and caudate nucleus [7].
  • Preliminary investigation revealed that during development BDNF and NT-3 are each expressed in several GI tract regions, and that their expression patterns overlap in some tissues, but are distinct in others [10].
  • These results provide a basis for targeting BDNF or NT-3 knockouts to specific GI tract tissues, and potentially altering vagal afferent innervation only in that tissue (e.g., smooth muscle vs. mucosa) [10].
  • Stratified squamous cell membranes contained NT3 [12].
  • The nucleus contained NT3 and cytosol contained NT4 [12].

Associations of NT3 with chemical compounds

  • Brimonidine treatment gave an increase in BDNF, NT3 and CNTF levels compared to the vehicle treated group [13].
  • Basal [Ca(2+)](i), peak responses to all agonists, SOCE, and force responses to ACh and histamine were all significantly enhanced by both acute and prolonged BDNF exposure (smaller effect of NT4) but decreased by NT3 [14].
  • Polypyrrole (Ppy) doped with p-toluene sulphonate (pTS) is an electroactive polymer into which neurotrophin-3 (NT3) can be incorporated [15].
  • In order to determine the possible susceptibility of naturally occurring ribonucleoside 3'-diphosphates, such as guanosine tetraphosphate (ppGpp), to 3'-phosphohydrolase activities, the 3'-nucleotidase was also employed in the attempted pyrophosphorolysis of adenosine 3'-diphosphate and guanosine tetraphosphate [16].
  • At the anatomical level, hydrogel/NT-3-treated animals showed far greater axon growth than controls in two major descending pathways for motor control, the CST and the raphespinal tract [17].

Analytical, diagnostic and therapeutic context of NT3


  1. Neurotrophin-3 expression in human pancreatic cancers. Ohta, T., Numata, M., Tsukioka, Y., Futagami, F., Kayahara, M., Kitagawa, H., Nagakawa, T., Yamamoto, M., Wakayama, T., Kitamura, Y., Terada, T., Nakanuma, Y. J. Pathol. (1997) [Pubmed]
  2. Alteration of lithium pharmacology through manipulation of phosphoadenosine phosphate metabolism. Spiegelberg, B.D., Dela Cruz, J., Law, T.H., York, J.D. J. Biol. Chem. (2005) [Pubmed]
  3. Inducible expression of suicide genes in Leishmania donovani amastigotes. Ghedin, E., Charest, H., Zhang, W.W., Debrabant, A., Dwyer, D., Matlashewski, G. J. Biol. Chem. (1998) [Pubmed]
  4. Expression of neurotrophin-3 promotes axonal plasticity in the acute but not chronic injured spinal cord. Chen, Q., Zhou, L., Shine, H.D. J. Neurotrauma (2006) [Pubmed]
  5. Enzyme regulation in a trypanosomatid: effect of purine starvation on levels of 3'-nucleotidase activity. Gottlieb, M. Science (1985) [Pubmed]
  6. Activity of wheat seedling nuclease toward single-stranded nucleic acids. Kroeker, W.D., Hanson, D.M., Fairley, J.L. J. Biol. Chem. (1975) [Pubmed]
  7. Ciliary neurotrophic factor (CNTF) genotypes: influence on choline acetyltransferase (ChAT) and acetylcholine esterase (AChE) activities and neurotrophin 3 (NT3) concentration in human post mortem brain tissue. Thome, J., Nara, K., Foley, P., Michel, T., Gsell, W., Retz, W., Rosler, M., Riederer, P. Journal für Hirnforschung. (1997) [Pubmed]
  8. Meta-analyses of the association between genetic polymorphisms of neurotrophic factors and schizophrenia. Lin, P.Y., Tsai, G. Schizophr. Res. (2004) [Pubmed]
  9. Tyrosine kinase inhibitor CEP-701 blocks the NTRK1/NGF receptor and limits the invasive capability of prostate cancer cells in vitro. Festuccia, C., Muzi, P., Gravina, G.L., Millimaggi, D., Speca, S., Dolo, V., Ricevuto, E., Vicentini, C., Bologna, M. Int. J. Oncol. (2007) [Pubmed]
  10. A genetic approach for investigating vagal sensory roles in regulation of gastrointestinal function and food intake. Fox, E.A. Autonomic neuroscience : basic & clinical. (2006) [Pubmed]
  11. Neurotrophins and other growth factors in the generation of retinal neurons. Frade, J.M., Bovolenta, P., Rodríguez-Tébar, A. Microsc. Res. Tech. (1999) [Pubmed]
  12. Role of neurotrophins and neurotrophin receptors in rat conjunctival goblet cell secretion and proliferation. Ríos, J.D., Ghinelli, E., Gu, J., Hodges, R.R., Dartt, D.A. Invest. Ophthalmol. Vis. Sci. (2007) [Pubmed]
  13. The growth factor response in ischemic rat retina and superior colliculus after brimonidine pre-treatment. L??nngren, U., N??p??nkangas, U., Lafuente, M., Mayor, S., Lindqvist, N., Vidal-Sanz, M., Hallb????k, F. Brain Res. Bull. (2006) [Pubmed]
  14. Neurotrophin effects on intracellular Ca2+ and force in airway smooth muscle. Prakash, Y.S., Iyanoye, A., Ay, B., Mantilla, C.B., Pabelick, C.M. Am. J. Physiol. Lung Cell Mol. Physiol. (2006) [Pubmed]
  15. The effect of polypyrrole with incorporated neurotrophin-3 on the promotion of neurite outgrowth from auditory neurons. Richardson, R.T., Thompson, B., Moulton, S., Newbold, C., Lum, M.G., Cameron, A., Wallace, G., Kapsa, R., Clark, G., O'leary, S. Biomaterials (2007) [Pubmed]
  16. Hydrolysis of ribonucleoside 3'-diphosphates by rye grass 3'-nucleotidase. Hecht, S.M., Hawrelak, S.D. Biochemistry (1975) [Pubmed]
  17. An injectable, biodegradable hydrogel for trophic factor delivery enhances axonal rewiring and improves performance after spinal cord injury. Piantino, J., Burdick, J.A., Goldberg, D., Langer, R., Benowitz, L.I. Exp. Neurol. (2006) [Pubmed]
  18. Dissection of the functional domains of the Leishmania surface membrane 3'-nucleotidase/nuclease, a unique member of the class I nuclease family. Debrabant, A., Ghedin, E., Dwyer, D.M. J. Biol. Chem. (2000) [Pubmed]
  19. Isolation and characterization of the gene encoding the surface membrane 3'-nucleotidase/nuclease of Leishmania donovani. Debrabant, A., Gottlieb, M., Dwyer, D.M. Mol. Biochem. Parasitol. (1995) [Pubmed]
  20. Purification and characterization of the 3'-nucleotidase/nuclease from promastigotes of Leishmania donovani. Campbell, T.A., Zlotnick, G.W., Neubert, T.A., Sacci, J.B., Gottlieb, M. Mol. Biochem. Parasitol. (1991) [Pubmed]
  21. Purification and characterization of a nuclease from Lentinus edodes. Shimada, H., Inokuchi, N., Koyama, T., Irie, M. Chem. Pharm. Bull. (1991) [Pubmed]
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