Summary

There is considerable evidence to support a role for neurotrophins as a strategy for treating chronic neurodegenerative conditions causing dementia, especially Alzheimer's disease and probably others including senile dementia of Lewy body type. In particular, a wealth of animal and tissue culture research points to the potential of nerve growth factor (NGF) as a means of supporting subcortical cholinergic cells, thereby retarding the disease process. Very early pilot work in human subjects has already been undertaken and attempts are under way to try and improve the drug delivery systems needed to allow such peptides to enter the brain and reach their predominantly subcortical targets. If successful, this approach would have a wider application to a number of neurodegenerative disorders, not necessarily confined to cholinergic cell systems.

Introduction

The concept of neurotrophic support for developing neurons was first suggested in the 1950s when Levi-Montalcini described the effect of transplanted mouse sarcoma tissue on the developing sensory and sympathetic nervous system of chick embryos. (This is reviewed by Levi-Montalcini, 1987.) Work in this field has moved on rapidly, especially in the last five years, and now much is known about a whole family of neurotrophic molecules and also their receptor systems in both normal development and disease. It is clear that members of this family can act in a neuroprotective role in the central as well as the peripheral nervous system. NGF and its receptors are the neurotrophin system most explored, especially in relation to Alzheimer's disease (AD), as far as dementia is concerned.