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Signalling for Survival: Potential Applications of Signal-Transduction Therapies for Suppression of Apoptosis in the Nervous System

  • Aviva M. Tolkovsky
Part of the GWUMC Department of Biochemistry and Molecular Biology Annual Spring Symposia book series (GWUN)

Abstract

One of the prime aims of therapies for neurodegenerative disorders is to find ways of preventing neuronal cell death. At the basis of this quest lie two major questions: (i) what is the molecular basis of death, with particular reference to death commitment point, and (ii) how can this process be prevented or slowed down? Some clues to these mechanisms can be obtained by studying neurons from the developing peripheral nervous system, where a process of limited death occurs when the amount and location of innervation are being matched to the requirements of the targets1. It was within this context that the discovery of the first nerve cell survival factor, NGF, was made by Levi-Montalcini and colleagues2. Since that time, several other neuronal survival factors have been discovered and it is now well established that neuronal survival factors include not only the NGF-family of neurotrophins (NGF, BDNF, NT3, and NT4/5) but also a range of cytokines and other polypeptide growth factors3. Moreover, some adult neurons may produce their own survival factors by autocrine or paracrine mechanisms/Despite these exciting advances, and the breakthroughs that have come with the identification of the trk family of receptors which mediate the actions of each of the neurotrophins4, it is still not known how survival factors signal for survival. Here, I summarise some of our studies on the mechanisms used by NGF-dependent superior cervical ganglion (SCG) neurons to prepare for death commitment point and outline possible mechanisms that may be utilised for preventing their death due to survival-factor-deprivation. Three main concepts are discussed:
  1. 1.

    That rescue by NGF and other survival factors may be mediated by post-translational mechanisms.

     
  2. 2.

    That parallel survival signalling pathways exist, some of which may not require the activation of cell-surface receptors.

     
  3. 3.

    That it may take longer for NGF to rescue neurons than the time its takes for NGF to initiate signalling cascades.

     

Keywords

Nerve Growth Factor Neuronal Cell Death Sympathetic Neuron Superior Cervical Ganglion Young Neuron 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Aviva M. Tolkovsky
    • 1
  1. 1.Department of BiochemistryUniversity of CambridgeCambridgeUK

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