Nerve growth factor and the neurotrophic factor hypothesis

Brain Dev. Sep-Oct 1996;18(5):362-8. doi: 10.1016/0387-7604(96)00051-4.


The discovery of nerve growth factor (NGF) over 40 years ago led to the formulation of the "Neurotrophic Factor Hypothesis". This hypothesis states that developing neurons compete with each other for a limited supply of a neurotrophic factor (NTF) provided by the target tissue. Successful competitors survive; unsuccessful ones die. Subsequent research on NTFs has shown that NTF expression and actions are considerably more complex and diverse than initially predicted. Even for NGF, different regulatory patterns are seen for different neuronal populations. As would be predicted by the "Neurotrophic Factor Hypothesis", NGF levels critically regulate basal forebrain cholinergic neuron size and neurochemical differentiation. In contrast, the level of trkA, the NGF receptor, regulates these properties in caudate-putamen cholinergic neurons. Understanding NTF regulation and actions on neurons has led to their use in clinical trials of human neurological diseases. NTFs may emerge as important therapies to prevent neuronal dysfunction and death.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / growth & development
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Humans
  • Nerve Growth Factors / biosynthesis
  • Nerve Growth Factors / physiology*
  • Nerve Growth Factors / therapeutic use
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / physiology*
  • Nerve Tissue Proteins / therapeutic use
  • Nervous System Diseases / pathology


  • Nerve Growth Factors
  • Nerve Tissue Proteins