Comparison of mammalian, chicken and <i>Xenopus</i> brain‐derived neurotrophic factor coding sequences

Isackson, Paul J.; Towner, Melvin D.; Huntsman, Molly M.

doi:10.1016/0014-5793(91)80812-h

Cited by 37 publications

(4 citation statements)

References 30 publications

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“…IA). The predicted amino acid sequence of the mature chicken NT-3 protein was then compared to that of chicken NGF (Ebendal er al., 1986) and chicken BDNF (Isackson et al, 1991) and shown to be 60.1 and 58.1 % identical to chicken NGF and BDNF, respectively ( Fig. 1B).…”

Section: Isolation Of Chicken Bdnf and Nt-3 Genesmentioning

confidence: 83%

Cellular Localization of Brain‐derived Neurotrophic Factor and Neurotrophin‐3 mRNA Expression in the Early Chicken Embryo

Hallböök

Ibáñez

Ebendal

et al. 1993

Eur J of Neuroscience

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Degenerate primers from conserved regions in nerve growth factor, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) were used in the polymerase chain reaction to isolate DNA fragments from the chicken BDNF and NT-3 genes. A genomic clone coding for chicken NT-3 was isolated and the structure of the chicken NT-3 mature protein was subsequently deduced from nucleotide sequence analysis of the isolated chicken NT-3 gene. Comparison of the chicken BDNF and NT-3 with the corresponding rat molecules showed that the avian molecules are very similar to their mammalian homologues. Northern blot analyses of messenger RNA (mRNA) from chicken embryos from embryonic day 3.5 (E3.5), E4.5, E8, E12 and E18 showed that expression of both BDNF and NT-3 mRNA peaked at E4.5 and decreased at later stages of development. Both probes revealed two transcripts; larger mRNAs of 4.5 kilobases (kb) for BDNF and 4.0 kb for NT-3 predominated over the smaller transcripts of 1.4 and 1.3 kb, respectively. The cellular localization of BDNF and NT-3 mRNA in the E4 and E6 embryos was studied by in situ hybridization. In the E4 embryo, labelling for BDNF was seen over cells in restricted parts of the epithelium of the otic vesicle. Analysis of adjacent sections for the low-affinity nerve growth factor receptor mRNA showed that regions in the otic vesicle epithelium which labelled for BDNF mRNA also labelled for low-affinity nerve growth factor receptor mRNA. No labelling for NT-3 was detected in the otic vesicle. Labelling for BDNF mRNA was also found over mesenchyme dorsal to the wing bud, in the wing bud and in the splanchnopleural lining of the stomach. Labelling for NT-3 mRNA was found at E4 over the epidermis on the ventral side in the region of the branchial arches. The labelling extended up the maxillary processes to Rathke's pouch. The closely located infundibulum was weakly labelled for NT-3 mRNA. NT-3 mRNA was also detected in the mesenchyme surrounding the oesophagus and lung buds. The regional expression pattern is in agreement with the established role for BDNF and NT-3 as target-derived neurotrophic factors, but the results also suggest that BDNF may be an intrinsic factor important for the development of the inner ear. The results support the emerging view that neurotrophic factors can play a role in early differentiation of both neuronal and non-neuronal tissues.

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Section: Isolation Of Chicken Bdnf and Nt-3 Genesmentioning

confidence: 83%

Cellular Localization of Brain‐derived Neurotrophic Factor and Neurotrophin‐3 mRNA Expression in the Early Chicken Embryo

Hallböök

Ibáñez

Ebendal

et al. 1993

Eur J of Neuroscience

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“…Under physiological conditions, the processing from pro-BDNF to mBDNF is important for neuronal development, neuronal survival, and synaptic plasticity. The mBDNF and its receptor, TrkB, are widely expressed in the developing and adult mammalian brains [ 173 , 174 ]. The pathways associated with changes in neuronal excitability are triggered by the binding of mBDNF to TrkB, indicating that TrkB activation is crucial for controlling the survival, morphogenesis, and plasticity of neurons [ 175 ].…”

Section: Potential Mechanisms Underlying Bdnf’s Effect On Admentioning

confidence: 99%

Brain-derived neurotrophic factor in Alzheimer’s disease and its pharmaceutical potential

Gao

Zhang

Sterling

et al. 2022

Transl Neurodegener

234

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Synaptic abnormalities are a cardinal feature of Alzheimer’s disease (AD) that are known to arise as the disease progresses. A growing body of evidence suggests that pathological alterations to neuronal circuits and synapses may provide a mechanistic link between amyloid β (Aβ) and tau pathology and thus may serve as an obligatory relay of the cognitive impairment in AD. Brain-derived neurotrophic factors (BDNFs) play an important role in maintaining synaptic plasticity in learning and memory. Considering AD as a synaptic disorder, BDNF has attracted increasing attention as a potential diagnostic biomarker and a therapeutical molecule for AD. Although depletion of BDNF has been linked with Aβ accumulation, tau phosphorylation, neuroinflammation and neuronal apoptosis, the exact mechanisms underlying the effect of impaired BDNF signaling on AD are still unknown. Here, we present an overview of how BDNF genomic structure is connected to factors that regulate BDNF signaling. We then discuss the role of BDNF in AD and the potential of BDNF-targeting therapeutics for AD.

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“…BDNF has been cloned from pig, mouse, rat, and human (Leibrock et al, 1989;Hofer et al, 1990;Maisonpierre et al, 1991). Partial sequence is known also from chicken and Xenopus (Hallbook et al, 1991;Isackson et al, 1991).…”

Section: The Members Of the Ngf Gene Familymentioning

confidence: 99%

Function and evolution in the NGF family and its receptors

Ebendal

1992

J of Neuroscience Research

326

146

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The gene family of neurotrophins includes nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4). Recently, neurotrophin-5 (NT-5), a possible mammalian homologue to NT-4 described in the frog Xenopus, has been cloned in man and rat. The neurotrophins stimulate survival and differentiation of a range of target neurons by binding to cell surface receptors. The structure of NGF has recently been clarified from crystallographic data. The similarities between the different neurotrophins are substantial with the variable regions, giving specificity to each of the family members, being localized to some exposed loop regions. Low-affinity binding (Kd of 10(-9) M) of all tested neurotrophins is mediated via a 75 K glycoprotein (LNGFR) that has been cloned and characterized. A 140 K tyrosine protein kinase encoded by the proto-oncogene trk has been found to bind NGF with high affinity (Kd of 10(-11) M) and to evoke the cellular neurotrophic responses. In addition, a protein encoded by the trk-related gene trkB has been shown to bind BDNF. Recently, a third member of the trk family, trkC, has been cloned and demonstrated to function as a high-affinity receptor for NT-3. The expression of trk and LNGFR mRNA are co-localized in the rat brain to the medial septal nucleus and the nucleus of Broca's diagonal band containing the NGF-responsive magnocellular cholinergic neurons projecting to hippocampus and cerebral cortex. In sharp contrast, the pattern of expression of trkB is widely spread in many areas of the cortex as well as lateral septum. The trkB protein might serve general functions in large areas of the cortex. Site-directed mutagenesis and expression of recombinant chimaeric neurotrophin proteins have made it possible to localize a likely region for the interaction between NGF and the LNGFR. This region could be altered, resulting in the total loss of LNGFR binding by the mutant NGF protein without affecting the binding to the trk receptor which was sufficient for the full biological activity. Cladistic analysis of likely phylogenies within the neurotrophins shows BDNF and NT-4 to be most closely related whereas NGF may be the sister group to NT-3, BDNF, and NT-4. Neurotrophins offer obvious clinical possibilities for treatment of neurodegenerative diseases.

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Comparison of mammalian, chicken and Xenopus brain‐derived neurotrophic factor coding sequences

Cited by 37 publications

References 30 publications

Cellular Localization of Brain‐derived Neurotrophic Factor and Neurotrophin‐3 mRNA Expression in the Early Chicken Embryo

Cellular Localization of Brain‐derived Neurotrophic Factor and Neurotrophin‐3 mRNA Expression in the Early Chicken Embryo

Brain-derived neurotrophic factor in Alzheimer’s disease and its pharmaceutical potential

Function and evolution in the NGF family and its receptors

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