Neurotrophic Factors: Versatile Signals for Cell-Cell Communication in the Nervous System

Abstract

Cell—cell communication is the main business of the cellular components of the nervous system. This dialogue is primarily based on layered system of molecules released and received by the different cell types that form the nervous system and its targets. At one level, neurotransmitter and neuromodulator substances dictate and propagate the activation states of neurons. In another layer, we find a group of regulatory molecules, typically poly­peptides of roughly a couple of hundred residues long, that control diverse aspects of the life of neurons, including survival, neuritic growth and dif­ferentiation states. Not surprisingly, many of these molecules have diverse functions also in tissues and organs outside the nervous system, where they are known as growth factors or cytokines. Although the term “neurotrophic factor” was originally associated with a survival-promoting activity, work on these molecules during the past ten years has considerably extended the functional spectrum of the term to comprise almost any growth factor or cytokine having some kind of effect on neurons. Important recent additions to the growing list of activities attributed to neurotrophic factors include short term effects on synaptic plasticity, growth cone steering and, quite paradoxically in retrospective, as active promoters of cell death. As much as cell—cell communication is of crucial importance for development, neuro­trophic factors play a central role during the assembly of the nervous system as regulators of cell number, axonal growth, target invasion and synaptic connectivity.