Motor neuron growth factors

The last 5 years have witnessed a great outgrowth in the number of clinical trials testing neuronal growth factors as potential treatments in ALS. These attempts to prevent motor neuron degeneration in ALS with the use of growth factors have their basis in the profound abilities of these molecules to affect motor neuron survival in experimental animals during early development and into maturity. Recent advances in molecular biology have led to the identification of a large number of new potential motor neuron growth factors Table 1, as well as insights into the molecular mechanisms regulating motor neuron death after growth factor deprivation. A major challenge in the field is now to select those growth factors that are the most promising for future ALS trials either alone or in combination therapy. View this table: Table 1. Motor neuron growth factors Two members of the prototypical family of nerve growth factors, the neurotrophins, are powerful modulators of motor neuron survival during development and into adulthood. The neurotrophin family in mammals comprises four members, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), molecules that share a significant degree of sequence homology. [1] An early indicator that one or more members of this neurotrophin growth factor family might affect motor neurons derived from experiments performed by Yan and colleagues. [2] These investigators demonstrated that motor neurons have the ability to retrogradely transport members of the neurotrophin family, including BDNF and NT-3, after these molecules have been injected into peripheral muscle. This experiment provided evidence that motor neurons express receptors for neurotrophins and might, in fact, respond to them. Localization studies have also demonstrated that skeletal muscle normally synthesizes neurotrophins (BDNF, NT-3, and NT-4) during the period of motor neuron innervation, during the maturation of synapse formation, and into adulthood. [3,4] …

[1]  P. Patterson,et al.  Cardiotrophin‐1 Induces the Same Neuropeptides in Sympathetic Neurons as Do Neuropoietic Cytokines , 1997, Journal of neurochemistry.

[2]  I. Fariñas,et al.  Renal and neuronal abnormalities in mice lacking GDNF , 1996, Nature.

[3]  Jonas Frisén,et al.  Renal agenesis and the absence of enteric neurons in mice lacking GDNF , 1996, Nature.

[4]  A. Buj-Bello,et al.  Characterization of a multicomponent receptor for GDNF , 1996, Nature.

[5]  J. Louis,et al.  GDNF–Induced Activation of the Ret Protein Tyrosine Kinase Is Mediated by GDNFR-α, a Novel Receptor for GDNF , 1996, Cell.

[6]  E. Arenas,et al.  Functional receptor for GDNF encoded by the c-ret proto-oncogene , 1996, Nature.

[7]  B. Wold,et al.  Know Your Neighbors: Three Phenotypes in Null Mutants of the Myogenic bHLH Gene MRF4 , 1996, Cell.

[8]  Austin G Smith,et al.  Essential function of LIF receptor in motor neurons , 1995, Nature.

[9]  S. Lehrman.  ... but seeks 'practical' gene therapy deals , 1995, Nature.

[10]  M. Dubois‐Dauphin,et al.  Bcl-2 overexpression prevents motoneuron cell body loss but not axonal degeneration in a mouse model of a neurodegenerative disease , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[11]  R. Vejsada,et al.  Mice lacking the CNTF receptor, unlike mice lacking CNTF, exhibit profound motor neuron deficits at birth , 1995, Cell.

[12]  L Li,et al.  Rescue of adult mouse motoneurons from injury-induced cell death by glial cell line-derived neurotrophic factor. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[13]  J. Martinou,et al.  Function and expression of the Bcl-x gene in the developing and adult nervous system , 1995, Neuroreport.

[14]  John Calvin Reed,et al.  Upregulation of bax protein levels in neurons following cerebral ischemia , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[15]  Z. Oltvai,et al.  Multiple Bcl-2 family members demonstrate selective dimerizations with Bax. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[16]  R. Oppenheim,et al.  Peptide inhibitors of the ice protease family arrest programmed cell death of motoneurons in vivo and in vitro , 1995, Neuron.

[17]  C F Ibáñez,et al.  Muscle-derived neurotrophin-4 as an activity-dependent trophic signal for adult motor neurons. , 1995, Science.

[18]  R. Vejsada,et al.  Neuronal deficits, not involving motor neurons, in mice lacking BDNF and/or NT4 , 1995, Nature.

[19]  W. Wood,et al.  Cardiotrophin-1 , 1995, The Journal of Biological Chemistry.

[20]  Sharad Kumar,et al.  ICE-like proteases in apoptosis. , 1995, Trends in biochemical sciences.

[21]  D. Choi,et al.  Potentiated necrosis of cultured cortical neurons by neurotrophins. , 1995, Science.

[22]  S. Korsmeyer.  Regulators of cell death. , 1995, Trends in genetics : TIG.

[23]  K. Chien,et al.  Expression cloning of cardiotrophin 1, a cytokine that induces cardiac myocyte hypertrophy. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[24]  D. Kleinfeld,et al.  BDNF and NT-4/5 exert neurotrophic influences on injured adult spinal motor neurons , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[25]  R. Oppenheim,et al.  Developing motor neurons rescued from programmed and axotomy-induced cell death by GDNF , 1995, Nature.

[26]  R. Taussig,et al.  Mammalian Membrane-bound Adenylyl Cyclases (*) , 1995, The Journal of Biological Chemistry.

[27]  C. Macilwain.  US National Cancer Institute chief quits , 1995, Nature.

[28]  J. Daly.  The chemistry of poisons in amphibian skin. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[29]  T. Eisner,et al.  Chemical ecology. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[30]  R. Vejsada,et al.  Quantitative Comparison of the Transient Rescue Effects of Neurotrophic Factors on Axotomized Motoneurons In Vivo , 1995, The European journal of neuroscience.

[31]  M. Segal,et al.  Morphological analysis of dendritic spine development in primary cultures of hippocampal neurons , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[32]  D. Chong,et al.  The Relationship Between Glycine and Gephyrin in Synapses of the Rat Spinal Cord , 1995, The European journal of neuroscience.

[33]  John Calvin Reed,et al.  Immunohistochemical determination of in vivo distribution of Bax, a dominant inhibitor of Bcl-2. , 1994, The American journal of pathology.

[34]  Z. Oltvai,et al.  Checkpoints of dueling dimers foil death wishes , 1994, Cell.

[35]  K. Kinzler,et al.  Has the breast cancer gene been found? , 1994, Cell.

[36]  Jean-Claude Martinou,et al.  Overexpression of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia , 1994, Neuron.

[37]  Q. Yan,et al.  The biological responses of axotomized adult motoneurons to brain- derived neurotrophic factor , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[38]  J. Cedarbaum,et al.  Arrest of motor neuron disease in wobbler mice cotreated with CNTF and BDNF. , 1994, Science.

[39]  R. Oppenheim,et al.  Neurotrophic agents prevent motoneuron death following sciatic nerve section in the neonatal mouse. , 1994, Journal of neurobiology.

[40]  D. V. Essen,et al.  Neural mechanisms of form and motion processing in the primate visual system , 1994, Neuron.

[41]  R. Jaenisch,et al.  Lack of neurotrophin-3 leads to deficiencies in the peripheral nervous system and loss of limb proprioceptive afferents , 1994, Cell.

[42]  G. Yancopoulos,et al.  Neurotrophic factors and their receptors , 1994, Annals of neurology.

[43]  D. Price,et al.  Neurotrophin 4/5 is a trophic factor for mammalian facial motor neurons. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[44]  M. Dubois‐Dauphin,et al.  Neonatal motoneurons overexpressing the bcl-2 protooncogene in transgenic mice are protected from axotomy-induced cell death. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[45]  Tom Maniatis,et al.  Transcriptional activation: A complex puzzle with few easy pieces , 1994, Cell.

[46]  D. Price,et al.  Ventral root avulsion: An experimental model of death of adult motor neurons , 1994, The Journal of comparative neurology.

[47]  I. Fariñas,et al.  Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development , 1994, Cell.

[48]  M. Barbacid,et al.  Disruption of the neurotrophin-3 receptor gene trkC eliminates la muscle afferents and results in abnormal movements , 1994, Nature.

[49]  S. Korsmeyer,et al.  bcl-2 protein expression is widespread in the developing nervous system and retained in the adult PNS. , 1994, Development.

[50]  V. Grant,et al.  Modes and origins of mechanical and ethological isolation in angiosperms. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[51]  H. Thoenen,et al.  Members of several gene families influence survival of rat motoneurons in vitro and in vivo , 1993, Journal of neuroscience research.

[52]  K. Rex,et al.  Influences of neurotrophins on mammalian motoneurons in vivo. , 1993, Journal of neurobiology.

[53]  M. E. Lewis,et al.  Insulin-like Growth Factor-I: Potential for Treatment of Motor Neuronal Disorders , 1993, Experimental Neurology.

[54]  J. Baker,et al.  Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r) , 1993, Cell.

[55]  Elizabeth J. Robertson,et al.  Role of insulin-like growth factors in embryonic and postnatal growth , 1993, Cell.

[56]  B. Turner.  Decoding the nucleosome , 1993, Cell.

[57]  H. Thoenen,et al.  Disruption of the CNTF gene results in motor neuron degeneration , 1993, Nature.

[58]  S. Korsmeyer,et al.  Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell death , 1993, Cell.

[59]  G. Yancopoulos,et al.  LIFR beta and gp130 as heterodimerizing signal transducers of the tripartite CNTF receptor. , 1993, Science.

[60]  P. Brûlet,et al.  Leukaemia inhibitory factor is necessary for maintenance of haematopoietic stem cells and thymocyte stimulation , 1993, Nature.

[61]  C. Macilwain.  Study proves Iraq used nerve gas , 1993, Nature.

[62]  H. Thoenen,et al.  Evidence that fibroblast growth factor 5 is a major muscle-derived survival factor for cultured spinal motoneurons , 1993, Neuron.

[63]  Nancy Y. Ip,et al.  The α component of the CNTF receptor is required for signaling and defines potential CNTF targets in the adult and during development , 1993, Neuron.

[64]  A. Abbott.  New biology institute in Milan prizes quality above loyalty in effort to become world-class , 1992, Nature.

[65]  P. Ernfors,et al.  Cells Expressing mRNA for Neurotrophins and their Receptors During Embryonic Rat Development , 1992, The European journal of neuroscience.

[66]  W. Snider,et al.  Axotomy-induced neuronal death during development. , 1992, Journal of neurobiology.

[67]  H. Thoenen,et al.  Ciliary neurotrophic factor prevents degeneration of motor neurons in mouse mutant progressive motor neuronopathy , 1992, Nature.

[68]  J. Mervis.  Panel trims NSF budget , 1992, Nature.

[69]  J. Lubischer,et al.  Transient and permanent effects of androgen during synapse elimination in the levator ani muscle of the rat. , 1992, Journal of neurobiology.

[70]  K. Unsicker,et al.  CNTF rescues motoneurons from ontogenetic cell death in-vivo, but not in-vitro. , 1990, Neuroreport.

[71]  H. Thoenen,et al.  Ciliary neurotrophic factor prevents the degeneration of motor neurons after axotomy , 1990, Nature.

[72]  P. Caroni,et al.  Nerve sprouting in innervated adult skeletal muscle induced by exposure to elevated levels of insulin-like growth factors , 1990, The Journal of cell biology.

[73]  W. Sossin,et al.  Sorting within the regulated secretory pathway occurs in the trans- Golgi network , 1990, The Journal of cell biology.

[74]  H. Horvitz,et al.  Genetic control of programmed cell death in the nematode C. elegans , 1986, Cell.

[75]  S. Korsmeyer,et al.  Cloning the chromosomal breakpoint of t(14;18) human lymphomas: clustering around Jh on chromosome 14 and near a transcriptional unit on 18 , 1985, Cell.

[76]  H. Schmalbruch,et al.  Motoneuron death after sciatic nerve section in newborn rats , 1984, The Journal of comparative neurology.

[77]  M. Matzke,et al.  Homology-dependent gene silencing in transgenic plants: what does it really tell us? , 1995, Trends in genetics : TIG.

[78]  T. Smyrk.  Colon cancer connections. Cancer syndrome meets molecular biology meets histopathology. , 1994, The American journal of pathology.

[79]  R. Levine,et al.  Dendritic reorganization of an identified neuron during metamorphosis of the moth Manduca sexta: the influence of interactions with the periphery. , 1993, Journal of neurobiology.