Why do neurons die when deprived of trophic factor?

In this commentary we present circumstantial evidence which supports the hypothesis that neuronal death produced by trophic factor deprivation (i.e., axotomy, target loss, etc.) is not a passive process resulting from a loss of trophic stimulation. Rather, we suggest that it is due to the activation of an endogenous "suicide program" requiring mRNA and protein synthesis. The possible mechanistic relationship of neuronal death to death of other cell types, both in the developing and adult organism, is discussed. If this hypothesis of active death is true, then loss of transcriptional control of this program may be involved in neuronal attrition in aging or neurodegenerative disease.