Neurotrophic factors in peripheral neuropathies: therapeutic implications

Neurotrophic factors are proteins which promote the survival of specific neuronal populations. Many have other physiological effects on neurons such as inducing morphological differentiation, enhancing nerve regeneration, stimulating neurotransmitter expression, and otherwise altering the physiological characteristics of neurons. These properties suggest that neurotrophic factors are highly promising as potential therapeutic agents for neurological disease. Neurotrophic factors will most likely be applied to the peripheral nervous system initially, since there are fewer problems for large proteins to gain access to peripheral neurons. Many of the most intensively studied factors are active in the peripheral nervous system. These include the neurotrophins (nerve growth factor, brain derived neurotrophic factor, neurotrophin-3, neurotrophin-4/5), the insulin like growth factors, ciliary neurotrophic factor, and glial cell derived neurotrophic factor and its related proteins. The biology of these factors and their receptors in the peripheral nervous system is reviewed here. We also review data suggesting that abnormal availability of some factors may contribute towards the pathogenesis of certain types of peripheral neuropathy. Finally, the pre-clinical data suggesting that individual factors might be effective in treating neuropathy is reviewed, along with data relating to possible side effects of neurotrophic factor therapy. Several factors have already entered clinical trials with variable success. The data from these trials is reviewed as well.