THE FAS RECEPTOR
ASSOCIATED WITH CELL DEATH IS A COMPONENT OF A SIGNALLING PATHWAY THAT INDUCES
AXON REGENERATION
Desbarats and his
colleagues[1]
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.
BM&L-March 2003
[1] Desbarats, J.,
et al. Fas engagement induces neurite growth through ERK activation and p35
upregulation. Nature Cell Biol. 5, 118-125, 2003.