THE FAS RECEPTOR ASSOCIATED WITH CELL DEATH IS A COMPONENT OF A SIGNALLING PATHWAY THAT INDUCES AXON REGENERATION
Desbarats and his colleagues have demonstrated that in a neuroblastoma cell line the Fas Receptor engagement activated the extracellular-signal regulated kinase (ERK) cascade, which is implicated in neurite outgrowth.
Fas was first identified in lymphocytes in which cross-linking of Fas receptors by the Fas ligand stimulates the cleavage of caspase 8. This event starts the caspase cascade, which ends in cell death. It has been previously demonstrated that in some neurons and glia, the engagement of Fas receptors by their ligand or Ab-Fas can have the opposite effect of stimulating growth. Studying two cell lines, a T-cell leukaemia line and a nuroblastoma line, the authors found that the receptor engagement in the first line activated caspase and in the second line promoted neurite outgrowth. They showed the mechanism also stimulated axon regeneration in vivo, in mice sciatic nerve functional recovery from crash injury.
We know that regeneration of axons after peripheral nerve injury depends on the activation of signalling pathways that induce neurite sprouting, thus Desbarats work is an important step toward the knowledge necessary to develop new treatments for nerve injury. Yet, some problems remain unsolved, among them the central question about the factors -except for the cell type- causing Fas to activate the caspase cascade rather than the ERK pathway: it seems that we need to learn more about the metabolic states of the cell influencing Fas activity.
 Desbarats, J., et al. Fas engagement induces neurite growth through ERK activation and p35 upregulation. Nature Cell Biol. 5, 118-125, 2003.