Fas-beyond death: a regenerative role for Fas in the nervous system

Fas (CD95, APO-1), a member of the TNF superfamily, is a prototypical "death receptor" which transduces apoptotic signals in a variety of cell types. However, cell death is not the only possible outcome of Fas signalling. Fas engagement by Fas Ligand can also trigger proliferation or differentiation, promote tumour progression and angiogenesis, and induce cytokine secretion and integrin expression. Recently, we have reported that Fas engagement induces a potent regenerative response in sensory neurons in vitro, and enhances peripheral nerve regeneration in vivo. In contrast, other types of neurons, notably motoneurons, are acutely sensitive to Fas-induced apoptosis. Here, we review the literature on non-apoptotic Fas signalling pathways, and discuss the potential roles, molecular mechanisms, and regulators of Fas signalling in the nervous system.