Neurotrophic factors

Neurotrophic factors constitute a group of cytokines that regulate the development, maintenance and survival of neurons, both in the central and peripheral nervous systems (Table 10.12). Although the first member of this family (NGF) was discovered more than 50 years ago, it is only in the last decade that the other members have been identified and characterized. The major subfamily of neurotrophic factors is the neurotrophins.

The original understanding of the term 'neurotrophic factor' was that of a soluble agent found in limiting quantities in the environment of sensitive neurons, and being generally manufactured by the neuronal target cells. It specifically promoted the growth and maintenance of those neurons. This description is now considered to be oversimplistic. Many neurotrophic factors are also synthesized by non-nerve target cells, and influence cells other than neurons (e.g. NGF is synthesized by mast cells and influences various cells of the immune system). Furthermore, various cytokines (including several growth factors; Table 10.12), discovered because of their ability to stimulate the growth of non-neuronal cells, are now also known to influence neuronal cells.

Each neurotrophic factor influences the growth and development of a specific group of neuronal types, with some cells being sensitive to several such factors. Many sustain specific neuronal populations whose death underlines various neurodegenerative diseases. This raises the possibility that these regulatory molecules may be of benefit in treating such diseases. Results from early clinical trials have been at best mixed, but many remain optimistic that neurotrophic factors may provide future effective treatments for some currently incurable neurodegenerative conditions.

Table 10.12 Molecules displaying neurotrophic activity in vivo and/or with neurons in culture




Neurotrophin-3 (NT-3) Neurotrophin-4/5 (NT 4/5) Neurotrophin-6 (NT-6)


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