Neurotrophins: a family of proteins supporting the survival of neurons

Abstract

NGF, BDNF, NT-3, and NT-4/5 are all members of a structurally related family of molecules that function to prevent the death of embryonic neurons during development. The presence of these molecules in the targets of innervating neurons is likely to explain at least in part why many neurons depend on their target tissues for survival. A small family of related membrane proteins with a ligand-activable tyrosine kinase and expressed in the nervous system represents a significant part of the structural basis explaining how neurons discriminate between the neurotrophins and transduce the consequence of neurotrophin binding. Thus, much structural information has been obtained that contributes to better understand some important aspects of vertebrate neurogenesis, particularly those related to selective cell survival in a very diverse cellular system like the nervous system. Future studies will have to explain how the role of these molecules has to be understood in the context of the characteristic features of the nervous system, in particular neurotransmission and electrical activity. Finally, while the role of neurotrophins has been discussed here in the context of the developing nervous system, it will be important to understand what functions these molecules might play in the central nervous system. For example, neurotrophins might function as long term mediators of changes in cellular shapes under the influence of electrical activity, as well as in pathological situations when axonal elongation is needed to restore connections, or to maintain the well-being of neurons that are eliminated during the course of neurodegenerative diseases.