Growth factors brain-derived neurotrophic factor

Nassenstein C, Braun A, Erpenbeck A, Lommatzsch M, et al. 2003. The neurotrophins nerve growth factors, brain derived neurotrophic factor, neurotrophin 3 and neurotrophin 4 are survival and activation factors for eosinophils in patients with allergic bronchial asthma. J Exp Med. 198 455-467. 

Another conceivable therapeutic approach for Alzheimer s disease could be based on the administration of neurotrophic factors. Nerve growth factor (NGF) is a 118 amino acid polypeptide with no blood-brain barrier penetrance. Other substances with neurotrophic activity such as epidermal growth factor, brain-derived neurotrophic factor, gangliosides, and the (11-28 peptide of the b-amyloid protein might also have a therapeutic potential. Intracerebroventricular (ICV) administration of NGF has been shown to partially reverse lesion-induced deficits of cortical AChE and choline acetyltransferase (CHAT) activities to promote survival of septal cholinergic neurons after fimbrial transection in adult rats and to reverse behavioral deterioration in rats with such lesions. 

Lindvall, O., Ernfors, P., Bengzon,J., Kokaia, Z., Smith, M. L., Siesjo, B. K., and Persson, H. (1992). Differential regulation of mRNAs for nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 in the adult rat brain following cerebral ischemia and hypoglycemic coma. Proc. Natl Acad. Sci USA 89, 648-652. 

The BBB is known to transport several cytokines in the blood-to-brain direction. For example, the BBB transports the IL-l s, IL-6, and TNF by three separate transport systems. Additionally, nerve growth factor, brain derived neurotrophic factor, interferons, neurotrophins, and leukemia inhibitory factor (Poduslo and Curran, 1996 Pan et al., 1997b Pan et al., 1998b Pan et al., 1998a) are also transported across the BBB. In some cases, the same gene which gives rise to a cytokine s receptor also produces the cytokine s transporter, whereas in other cases the receptor and transporter are immunologic ally distinct proteins (Banks and Kastin, 1992 Pan and Kastin,... 

Koliatsos, V. E., Price, D. L., Gouras, G. K., Cayouette, M. El., Burton, L. E., and Winslow, J. W., Highly selective effects of nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 on intact and injured basal forebrain magnocel-lular neurons, J. Comp. Neurol., 343, 247, 1994. 

Hohn, A., Leibrock, J., Bailey, K. and Barde, Y.A. (1990) Identification and characterization of a novel member of the nerve growth factor/brain derived neurotrophic factor family. Nature 344 339-341. 

Rocamora, N., Palacios, J.M. and Mengod, G. (1992) Limbic seizures induce a differential regulation of the expression of nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3, in the rat hippocampus. Mol. Brain Res. 13 27-33. 

Takeda, A., Onodera, H., Sugimoto, A., Kogure, K., Obinata, M. and Shibahara, S. (1993) Coordinated expression of messenger RNAs for nerve growth factor, brain derived neurotrophic factor and neurotrophin 3 in the rat hippocampus following transient forebrain ischemia. Neuroscience 55 23-31. 

BDNF (brain-derived neurotrophic factor) is a neuro-trophin, i.e. a target-derived growth factor, which is expressed in the brain predominantly in the hippocampus. It acts through its tyrosine kinase receptor, trkB,... 

FIGURE 2 7-2 Neurotrophin receptors. Neurotrophin family members bind specifically to cognate Trk receptors. The low affinity neurotrophin receptor, p75, promiscuously binds all neurotrophins. BDNF, brain-derived neurotrophic factor NGF, nerve growth factor NT, neurotrophin. 

Yamada, K. et al. (2002). Role for brain derived neurotrophic factor in learning and memory. Life Sci. 70(7), 735-744. Yamada, M. et al. (1997). The neurotrophic action and signalling of epidermal growth factor. Progr. Neurobiol. 51(1), 19-37. 

Growth cones are subject to both chemoattractant and chemorepellent effects of guidance molecules and also to attraction or repulsion resulting from cell cell-contacts. To complicate the picture further, the netrins and also the brain-derived neurotrophic factor BDNF (see Fig. 30-6D) may first attract, and then after a period of adaptation or desensitization, repel a growth cone.4 13 4 4 446 443 Consecutive phases of desensitization and resensitization may result in a zig zag path of... 

Zafra F., Castren E., Thoenen H., and Lindholm D. (1991). Interplay between glutamate and y-aminobutyric acid transmitter systems in the physiological regulation of brain-derived neurotrophic factor and nerve growth factor synthesis in hippocampal neurons. Proc. Natl. Acad. Sci.USA 88 10037-10041. 

Brain-derived neurotrophic factor (BDNF) exhibits distinct effects on survival, morphological differentiation, neuritic growth, protection against MPP+ cytotoxicity, and dopamine uptake... 

Inoue S, Susukida M, Ikeda K, Murase K, Hayashi K (1997) Dopaminergic transmitter up-regulation of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) synthesis in mouse astrocytes in culture. Biochem Biophys Res Common 235 468 472. 

Zafia F, Lindholm D, Casden E, Hardkka J, Thoenen H (1992) Reguladon of brain-derived neurotrophic factor and nerwe growth factor mRNA in primary cultures of hippocampal neurons and as d ocytes. J Neurosci 12 4793 799. 

BDNF brain derived neurotrophic factor is a member of the nerve growth factor family of trophic factors. In the brain, BDNF has a trophic action on retinal, cholinergic, and dopaminergic neurons, and in the peripheral nervous system it acts on both motor and sensory neurons. (From Kendrew, The Encyclopedia of Molecular Biology, 1994). 

Brain-Derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (Beta Polypeptide) (NGF) Genes... 

Sawai, H., Clarke, D. B., Kittlerova, P., Bray, G. M., andAguayo, A. J., Brain-derived neurotrophic factor and neurotrophin-4/5 stimulate growth of axonal branches from regenerating retinal ganghon cells, J. Neurosci., 16, 3887, 1996. 

Beck, K. D., Kniisel, B., and Hefti, F., The nature of the trophic action of brain-derived neurotrophic factor, des(l - 3) -insulin-like growth factor-1, and basic fibroblast growth factor on mesencephalic dopaminergic neurons developing in culture, Neuroscience, 52, 855, 1993. 

Nelson and Bauman (2003) measured numerous neuropeptides in archived neonatal blood of children later diagnosed with autism, mental retardation, cerebral palsy, and controls. They found, in comparison with controls, significant elevations in concentrations of vasointestinal peptide (VIP), calcitonin gene-related peptide (CGRP), brain-derived neurotrophic factor (BDNF), and nerve growth factors (NT4/5) in children with autism and in those with mental retardation without autism. There was no measure that distinguished autism from mental retardation. 

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