ABSTRACT
RAGE is a multiligand member of the immunoglobulin superfamily of cell surface molecules
whose properties extend the paradigm of ligand-receptor interactions. The receptor
recognizes families of ligands with diverse structural features, such as advanced
glycation endproducts (AGEs), amyloidogenic peptides/polypeptides, amphoterins, and
S100/calgranulins rather than individual species. Engagement of RAGE by its ligands
upregulates the receptor and initiates a cycle of sustained cellular perturbation;
increased levels of RAGE on the cell surface make it an ideal target for subsequent
ligand interactions and for propagating cellular dysfunction. At this time, the only
means known to break this apparently vicious cycle appears to be blocking access to
RAGE or removing the ligands. Taken together, these data suggest that RAGE has the
potential to function as a progression factor in a range of disorders (AGEs are relevant
to diabetes and other settings of oxidant stress, amyloidogenic peptides are relevant
to amyloidoses, S100/calgranulins are relevant to inflammatory disorders, etc.) in
which its ligands accumulate. The chronic juxtaposition of ligand and receptor triggers
sustained cellular perturbation favoring mechanisms eventuating in tissue injury rather
than those that would restore homeostasis.
KEYWORD
Advanced glycation endproduct - S100 proteins - calgranulins - amphoterins - amyloid
