Nerve growth factor (NGF) is an insulin-like protein, which regulates growth, development and maintenance of sympathetic and embryonic sensory neurons. It is found in varying amounts in the venom of all tested poisonous snakes and in the male mouse submaxillary gland. Its first interaction with target neurons is the binding to a cell surface receptor. The occurrence of internalized NGF as well as specific nuclear binding sites, however, suggest a mechanism of action not exclusively mediated through cell surface receptors. A model of the overall mechanism of action of NGF accommodating these observations is proposed. NGF has a variety of effects on the central nervous system (CNS) under experimental conditions: It enhances the regeneration of central adrenergic neurons and it brings forth temporal changes in surface specificity of cultured embryonic chick tectal cells. Furthermore, NGF specific binding sites are found in the synaptosomal fraction of homogenates of embryonic chick brain. In the unperturbed brain, however, no definitive role of the growth factor has been found, and the significance of NGF in the CNS is still an open question.Nerve Growth Factor (NGF) is the archetypal neurotrophin of a family of polypeptides that also includes brain derived neurotrophic factor, neurotrophin-3, and neurotrophin 4/5. NGF binds to and activates a receptor protein tyrosine kinase, Trk Kaplan et al (1991). Homozygous deletion of the Trk gene in mice demonstrated that NGF was required for many sensory and sympathetic neurons during development Smeyne et al (1994). These mice had neuronal cell loss in trigeminal, sympathetic and dorsal root ganglia, as well as a decrease in the cholinergic basal forebrain projections to the hippocampus and cortex. Homozygous deletion of NGF also demonstrated a requirement by sensory and sympathetic neurons for NGF, but surprisingly basal forebrain cholinergic neurons developed and differentiated normally Crowley et al (1994).

The history of the discovery of NGF is of interest. In 1951, Rita Montalcini and Viktor Hamburg published their ground breaking work on the discovery that a mouse tumor released a diffusible factor that promoted neurogenesis Levi-Montalcini and Hamburger (1951). Enlisting the help of a biochemist, Stanley Cohen, they successfully purified a growth promoting factor Cohen et al (1954), which would later be named NGF. The discovery marked the first identification of a growth factor and was recognized by the awarding of the Nobel Prize to Rita Montalcini and Stanley Cohen in 1986.

Nerve growth factor (NGF) is a member of a family of growth and survival factors known as neurotrophins. Although these factors were discovered because of their actions during development, they are now known to function throughout the life of the animal. NGF plays a prominent role in nociception because its selective receptor trkA is expressed primarily on nociceptors. Recent studies have demonstrated that it sensitizes the response to nociceptive stimuli via acute posttranscriptional mechanisms and by changing expression of numerous genes. These findings have led to promising clinical developments in pain biology. Other neurotrophins such as NT-3 and BDNF have also been studied extensively and are important determinants of structure and function in the central nervous system.

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John Mathews

Editorial Assistant

American Journal of Pharmacology and Pharmacotherapeutics