Molecular biology of neurotrophic factors

The survival and functional maintenance of spinal motoneurones and of peripheral neurones, such as sensory, sympathetic and parasympathetic neurones, has been shown to depend on neurotrophic factors, both during the period of developmental cell death and in adulthood. A variety of such factors has been identified over recent years, among them factors of the NGF gene family, for example BDNF, NT-3, NT-4/5 and NT-6, and factors such as CNTF and LIF acting on neuronal target cells via receptor components shared with cytokines such as IL-6. In addition, pluripotent mitogens, such as IGF-I and IGF-II can support the survival of a variety of neuronal cell types, including spinal motoneurones both in cell culture and in vivo. The establishment of mice in which the genes for these factors and their receptors have been inactivated by homologous recombination has been a major step in the understanding of their physiological function. It is not clear so far whether or not similar gene defects in human are associated with any neurological disease. However, some of these factors have been demonstrated to be effective in animal models of neuropathy and motoneurone disorders, so that first clinical trials using these factors for symptomatic treatment of amyotrophic lateral sclerosis (ALS) and peripheral neuropathies have already been initiated.