The role of presenilin and its interacting proteins in the biogenesis of Alzheimer's beta amyloid.
The biogenesis and accumulation of the beta amyloid protein (Abeta) is a key event in the cascade of oxidative and inflammatory processes that characterises Alzheimer's disease. The presenilins and its interacting proteins play a pivotal role in the generation of Abeta from the amyloid precursor protein (APP). In particular, three proteins (nicastrin, aph-1 and pen-2) interact with presenilins to form a large multi-subunit enzymatic complex (gamma-secretase) that cleaves APP to generate Abeta. Reconstitution studies in yeast and insect cells have provided strong evidence that these four proteins are the major components of the gamma-secretase enzyme. Current research is directed at elucidating the roles that each of these protein play in the function of this enzyme. In addition, a number of presenilin interacting proteins that are not components of gamma-secretase play important roles in modulating Abeta production. This review will discuss the components of the gamma-secretase complex and the role of presenilin interacting proteins on gamma-secretase activity.
Verdile
Giuseppe
G
Centre of Excellence for Alzheimer's Disease Research and Care, and the Sir James McCusker Alzheimer's Disease Research Unit, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, 100 Joondalup Drive, Joondalup, 6027 WA, Australia.
Gandy
Samuel E
SE
Martins
Ralph N
RN
D000544:Alzheimer Disease / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins; D053763:Presenilins / Q000502:physiology*; D011485:Protein Binding; D013379:Substrate Specificity
D016229:Amyloid beta-Peptides; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D029543:Nucleocytoplasmic Transport Proteins; D053763:Presenilins; C484395:TMED10 protein, human; C413604:nicastrin protein; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C475285:presenilinase, human