Purification and Microsequencing of Neurotrophic Proteins

Neurotrophic proteins have been broadly defined as those that promote the survival or differentiation of embryonic neurons. The first neurotrophic protein and the protein whose properties are responsible for this definition is nerve growth factor (NGF) (Cohn, 1960). In vivo, NGF participates directly in the regulation of programmed cell death by keeping neurons alive that would die in its absence. In cell culture systems, NGF is required for the survival of some cell-types and the differentiation of others. Additional in vivo experiments have demonstrated that NGF is synthesized in limiting amounts by the target tissues of the neurons that require it for survival. Finally, both in vitro and in vivo experiments show that NGF is cell-type specific in the sense that it promotes the survival and differentiation of only a few classes of neurons. These observations, in conjunction with the extreme cell-type heterogeneity of the nervous system, suggest that many other neurotrophic proteins remain to be discovered that have roles in the life, differentiation, and death of other subsets of cells. This conclusion has led to increasingly intense efforts to discover new neurotrophic molecules.