title: Presenilins and the gamma-secretase: still a complex problem.
abstract: The presenilins form part of a complex of membrane proteins that are involved in the proteolytic cleavage of cell-surface molecules. This article reviews the history of the discovery of the presenilins, their role in the pathogenesis of Alzheimer's disease and in the metabolism of the amyloid-beta precursor protein. Unanswered questions about their biochemical mechanism of action and their effects on Ca2+ homeostasis are examined.
authors.affiliation: Menzies Research Institute, University of Tasmania, Hobart, Tasmania 7001, Australia. d.h.small@menzies.utas.edu.au
authors.forename: David H
authors.initials: DH
authors.lastname: Small
authors.forename: David W
authors.initials: DW
authors.lastname: Klaver
authors.forename: Lisa
authors.initials: L
authors.lastname: Foa
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D009154:Mutation; D053763:Presenilins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D053763:Presenilins; D053829:Amyloid Precursor Protein Secretases; D002118:Calcium