Metabolism of presenilins.
Understanding mechanisms involved in the production of Abeta has long been the central focus of cell biologists engaged in molecular AD research. The discovery of two genes that encode homologous polytopic membrane proteins termed Presenilins (PS), has lead to several exciting recent findings on the proteolytic processes responsible for generating the COOH-terminus of Abeta. What we now know is that PS proteins play an important role in Abeta production and are considered one of the therapeutic targets. Here I have reviewed the vast literature on the biology of PS, especially focusing on PS endoproteolysis and the accumulation of stable PS derivatives that are likely the functional units.
Thinakaran
G
G
Department of Neurobiology, Pharmacology and Physiology, Center for Molecular Neurobiology, The University of Chicago, IL 60637, USA. gopal@uchicago.edu
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D020169:Caspases / Q000378:metabolism; D020134:Catalytic Domain / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D053764:Presenilin-1; D053766:Presenilin-2
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D010447:Peptide Hydrolases; D020169:Caspases