Neurotrophic Factors and Neuronal Death

The well-documented physiological role of nerve growth factor (NGF) in peripheral sympathetic and neural-crest-derived sensory neurons in vivo has its exact counterpart in vitro. This provided the conceptual basis for developing in vitro analytical procedures for the purification of new neurotrophic molecules. The experimental approaches used are discussed in the context of the purification of new neurotrophic factors, brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF). The importance of the modulatory role played by extracellular matrix molecules, in particular laminin, on both NGF-mediated and BDNF-mediated survival effects is also delineated. BDNF is a very basic (pI approximately 10) molecule of about 12 kDa, having physico-chemical characteristics close to those of the monomer of NGF. However, the spectrum of its biological actions is distinctly different from that of NGF. In particular, BDNF supports the survival of retinal ganglion cells and placode-derived peripheral sensory neurons which are not supported by NGF. The trophic supply of primary sensory neurons projecting to both the central nervous system and the periphery is discussed. It is hypothesized that sensory neurons receive limited quantities of neurotrophic molecules from both peripheral and central axons, a mechanism ensuring the survival of neurons adequately connected with both peripheral and central targets.