g-secretase, which has made it farthest as a drug target, still has an identity problem. One camp of researchers, including physician Dennis J. Selkoe, professor of neurologic diseases at Harvard Medical School, has put its money on presenilin1 (PS1),1 a molecule long associated with g-secretase activity. It is mutated in one form of early onset familial AD, which accounts for 5% to 10% of Alzheimer's cases. Selkoe says an upcoming paper, scheduled for publication in the Proceedings of the National Academy of Sciences, moves closer to showing that Presenilin-1 is indeed g-secretase.
But not everyone is completely convinced. Raphael Kopan, associate professor of medicine, molecular biology and pharmacology at Washington University in St. Louis, explains, "The absolute proof will, of course, require demonstration that you can isolate presenilin1 with the substrate, play some mood music ... and eventually cleavage will occur." Sangram Sisodia, director for the center of neurobiology at ...
