REGULATION OF APOPTOSIS BY PRESENILIN-1

Familial Alzheimer's disease is transmitted as an autosomal dominant d isorder and, in 5-10% of the cases, is caused by mutations in the codi ng regions of two homologous genes, Presenilin I and 2 (PS I and PS2). Previously, we have shown that PS2, a homolog of PS1, regulates apopt osis induced in neurons by trophic withdrawal or A beta, and in T-cell s by Fas ligand. We now report that PS1 also regulates apoptosis. Both wild-type and the H115Y mutant form of PS1 enhance Pas-mediated apopt osis in Jurkat cells. We also observed that wild-type and the H115Y mu tant form of PS1 differentially regulate Jun Kinase, an important enzy me regulating apoptosis. (C) 1998 Elsevier Science Inc.