Neurotrophic factors in peripheral neuropathies: pharmacological strategies

Peripheral neuropathy is defined as a derangement in structure and function of peripheral motor, sensory and autonomic neurones, and can involve either the entire neurone or selected parts of the neurone. Due to the complex and diverse nature of the neurone, there are many potential sites and mechanisms which can be influenced to provoke a dysfunctional state. The cellular and molecular mechanisms involved in the development of neuropathy are therefore diverse and only partially understood. Studies have been undertaken using many drugs and disease models to cause pathological insult to the nervous system resulting in experimental neuropathies. To some extent it is possible to correlate the locality of the pathological insult within the neurone to the type of neuropathy manifested. Nerve growth factor belongs to a family of neurotrophins implicated in the survival of many different types of neurones. Hence in the deranged nerve it could be envisaged that the there is a reduction in either the availability of NGF to the neurone or an impairment in the machinery transducing its response. One mechanism therefore would be the introduction of compounds into the system that cause the induction of NGF. To this end many compounds are under investigation in culture and in animals models to ascertain their effect on NGF with the view that such drugs can then be extrapolated to the human pathological condition. This review will describe the current state of research into the compounds that induce NGF, whilst recognising that the effects of NGF are selective for certain classes of neurone, but that similar mechanisms may operate for other neurotrophic factors with effects on a wider population of nerves.