Neurotrophins

Literature References: Family of highly conserved, target-derived, secretory proteins that promote the differentiation, growth, and survival of neurons in the peripheral and central nervous systems. Produced in limiting amounts by innervated tissues to enhance neuronal differentiation and survival. Five closely related factors have been identified: nerve growth factor (NGF), q.v., brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), NT-4, and NT-5. Neurotrophins differ in their sites of synthesis, developmental patterns of expression, and neuronal targets. Amino acid sequences are highly homologous. Most of the sequence differences are contained in 4 specific regions which are presumed to be responsible for the biological specificities of the factors. Purification of BDNF from pig brain: Y.-A. Barde et al., EMBO J. 1, 549 (1982). Cloning and expression of BDNF: J. Leibrock et al., Nature 341, 149 (1989). Identification of rat NT-3: P. C. Maisonpierre et al., Science 247, 1446 (1990); of human NT-3: Y. Kaisho et al., FEBS Lett. 266, 187 (1990); A. Rosenthal et al., Neuron 4, 767 (1990). Isolation of NT-4 from Xenopus laevis: F. Hallböök et al., ibid. 6, 845 (1991). Identification of NT-5 in rat and human: L. R. Berkemeier et al., ibid. 7, 857 (1991). Proposed identity of NT-5 as the mammalian homolog of Xenopus NT-4: N. Y. Ip et al., Proc. Natl. Acad. Sci. USA 89, 3060 (1992). Comparison of neurotrophins and other neurotrophic factors: H. Thoenen, Trends Neurosci. 14, 165 (1991). Discussion of neurotrophin receptors: S. O. Meakin, E. M. Shooter, ibid. 15, 323 (1992). Review of amino acid sequences and molecular structure: T. Ebendal, J. Neurosci. Res. 32, 461-470 (1992). Review of bioactivity and distribution in the nervous system: G. Vantini, Psychoneuroendocrinology 17, 401-410 (1992); of bioactivity and therapeutic potential in neurologic disease: F. F. Eide et al., Exp. Neurol. 121, 200-214 (1993).