NERVE GROWTH-FACTOR AND THE NEUROTROPHIC FACTOR HYPOTHESIS

The discovery of nerve growth factor (NGF) over 40 years ago led to th e formulation of the ''Neurotrophic Factor Hypothesis'', This hypothes is states that developing neurons compete with each other for a limite d supply of a neurotrophic factor (NTF) provided by the target tissue. Successful competitors survive; unsuccessful ones die. Subsequent res earch on NTFs has shown that NTF expression and actions are considerab ly more complex and diverse than initially predicted, Even for NGF, di fferent regulatory patterns are seen for different neuronal population s, As would be predicted by the ''Neurotrophic Factor Hypothesis'', NG F levels critically regulate basal forebrain cholinergic neuron size a nd neurochemical differentiation. In contrast, the level of trkA, the NGF receptor, regulates these properties in caudate-putamen cholinergi c neurons, Understanding NTF regulation and actions on neurons has led to their use in clinical trials of human neurological diseases, NTFs may emerge as important therapies to prevent neuronal dysfunction and death.