Disease relevance of NTF5

• The neurotrophins nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 are survival and activation factors for eosinophils in patients with allergic bronchial asthma [1].
• BDNF and NT-4 may have therapeutic implications for a variety of neurodegenerative diseases [2].
• NT4 staining was found to be less intense in lasered and melanoma controls compared to normal cadaveric donor retinas [3].
• We also have found that ligands for the trkB receptor (brain-derived neurotrophic factor and neurotrophin-4/5) acutely sensitize nociceptive afferents and elicit hyperalgesia [4].
• We have expressed, refolded, and purified recombinant human NT-4 from Escherichia coli and compared it with recombinant human NT-4 secreted into the culture medium of baculovirus-infected insect cells [5].

Psychiatry related information on NTF5

• Serum NT-4 concentration tended to be increased in the mental retardation group (P <0.05 by ANOVA) [6].
• To test this, we measured protein levels of nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin-4/5 in visual cortex of young (postnatal day 38-46, at the peak of the critical period) and adult ferrets with two-site enzyme-immunoassay systems [7].
• Cellular delivery of CNTF but not NT-4/5 prevents degeneration of striatal neurons in a rodent model of Huntington's disease [8].

High impact information on NTF5

• Many types of neurons in the central nervous system are excited by BDNF or neurotrophin-4/5, an action that has recently been implicated in synaptic plasticity [9].
• At vanishingly low concentrations, factors of the neurotrophin family (NGF, BDNF, NT3 and NT4/5) can promote neuronal survival or death [10].
• Recruitment of endothelial cells and promotion of channel formation within the Matrigel plug by BDNF and NT-4 was comparable to that induced by VEGF-A [11].
• Heterotopic neurons have the same birth date and phenotype as normal MZ neurons; they are not the result of NT4-induced proliferation or rescue from apoptosis [12].
• Neuronal heterotopias in the developing cerebral cortex produced by neurotrophin-4 [12].

Biological context of NTF5

• In the human, both NTF5 and NTF6 gene loci were mapped to chromosome 19 by Southern analysis of somatic cell hybrid panels [13].
• Mammalian neurotrophin-4: structure, chromosomal localization, tissue distribution, and receptor specificity [14].
• We found that acute administration of NT-4/5 to 7-day-old cultures stimulates the hydrolysis of phosphatidylinositol, an event involved in neurotrophin signal transduction [15].
• Growth of striatal cultures in the presence of NT-4/5 resulted in increased cell survival, as indicated by elevations in cell number, protein content, and a measure of mitochondrial enzyme activity (MTT assay) [15].
• NT-4/5 transiently supported mouse NGF-dependent trigeminal and jugular neurons at early stages of target field innervation and mouse brain-derived neurotrophic factor (BDNF)-dependent no-dose neurons during the phase of naturally occurring cell death [16].

Anatomical context of NTF5

• These data suggest that NT-4/5, like BDNF, promotes oocyte nuclear maturation [17].
• This study demonstrates for the first time that NT-4/5 and NT-3 are present in the follicular fluid of the human ovary [17].
• Levels of NT-4/5 and the NT-4/NT-3 ratio were slightly reduced in hippocampus and cerebellum in the group with AD compared with the control group (P<.05) [18].
• Expression of mRNA encoding neurotrophins and neurotrophin receptors in human granulocytes and bone marrow cells--enhanced neurotrophin-4 expression induced by LTB4 [19].
• Moreover, the inflammatory mediator leukotriene B4 (LTB4) up-regulated the expression of NT-4 mRNA in granulocytes, but did not affect the expression of other neurotrophin mRNAs [19].

Associations of NTF5 with chemical compounds

• NT-4/5 increased GABA uptake and staining intensity in these cultures, as indicated by GABA immunocytochemistry, indicating a trophic action on GABAergic neurons, the predominant neuron type in the striatum [15].
• This suggests that the autocrine expression of NGF, BDNF and NT-4/5 is up-regulated in prostate epithelial cells following their transformation to an androgen refractory pathology [20].
• At maximally effective concentrations, BDNF or NT-4 induced robust TrkB tyrosine phosphorylation at 5 min; this progressively declined at 15, 30, and 60 min [21].
• The NT4 repeated sequence LKTEN was highly homologous with a site conserved in cardiac myosins, the B repeat region peptides were 47% homologous to human cardiac myosin amino acid sequence, and the C3 sequence RRDL was identical to a highly conserved site in skeletal and cardiac myosins [22].
• Nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin-4/5 all significantly increased levels of substance P after either a 4 h or 20 h incubation in ganglia obtained at stages 33 and 44 [23].

Physical interactions of NTF5

• RESULTS: We have determined the 2.7 A crystal structure of neurotrophin-4/5 bound to the neurotrophin binding domain of its high-affinity receptor TrkB (TrkB-d5) [24].
• Moreover, neutralizing the activity of endogenous NGF with a specific blocking antibody, or antagonizing NGF binding to p75(NTR) by the application of human NT-4/5, reduces the levels of apoptotic cell death in both the sclerotome and the dermamyotome by about 50 and 70%, respectively [25].

Regulatory relationships of NTF5

• NT-4 was active in promoting the survival of rat TrkB receptor-expressing fibroblasts, but was inactive on embryonic chicken sensory neurons, unlike the other members of the neurotrophin family and in contrast to the reported activities of partially purified NT-4 [5].

Other interactions of NTF5

• The results suggest that neurotrophins may act as granulocyte-derived effector molecules and that human bone marrow cells may be targets for these compounds, in particular BDNF and NT-4 [19].
• Transcription of NT-4 was only detected in epithelium and transcription of GDNF only in stroma [26].
• As a single factor NT-4/5 produced the greatest increase in ChAT activity, but was not additive with any other neurotrophin or CNTF [27].
• NGF, NT-3 and NT-4 showed no significant differences within surviving neurons or neuropil [28].
• This occurs in parallel with an increased expression of GFAP suggesting that reactive changes in Muller cells may be responsible for reduced NT4 staining [3].

Analytical, diagnostic and therapeutic context of NTF5

• We describe the expression and purification of the second Ig-like domain of human TrkB (TrkBIg(2)) and show, using surface plasmon resonance, that this domain is sufficient to bind BDNF and NT-4 with subnanomolar affinity [2].
• CONCLUSION: NT4 is expressed in inner and outer nuclear layers of normal human retina and its expression is downregulated following laser photocoagulation [3].
• Northern blot analysis of different tissues from Xenopus showed NT-4 mRNA only in ovary, where it was present at levels over 100-fold higher than those of NGF mRNA in heart [29].
• Total RNA was extracted from the frozen ovarian samples, and the expression of NT-4/5, BDNF and the TrkB receptor (full length and two truncated isoforms) was investigated by RT-PCR [30].
• In agreement with the pattern of trk receptor expression, infusion of recombinant human BDNF or NT-4/5 into the vicinity of the axotomized RSNs, between days 7 and 14 after axotomy, fully prevented their atrophy [31].

References