Post-translational processing of beta-secretase in Alzheimer's disease.
Beta-amyloid is released into the brains of Alzheimer's patients, where it aggregates and causes damage to neurons. It is cleaved proteolytically from a large transmembrane glycoprotein amyloid precursor protein by a membrane-bound protease, known as beta-secretase identified previously as the acid protease, Asp-2. We have shown previously that beta-secretase is up-regulated by increased intracellular cholesterol, and down-regulated by cholesterol biosynthesis inhibition. Here we show using mass spectrometry that discrete changes in the glycosylation and palmitoylation of beta-secretase occur when cells expressing it are treated with statins.
Sidera
Christina
C
Department of Basic Medical Sciences, St. George's Hospital Medical School, London, UK.
Parsons
Richard
R
Austen
Brian
B
D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000924:Anticholesteremic Agents / Q000494:pharmacology; D016282:Aspartic Acid Endopeptidases; D002460:Cell Line; D002784:Cholesterol / Q000494:pharmacology; D010450:Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D006026:Glycoside Hydrolases / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008148:Lovastatin / Q000494:pharmacology; D013058:Mass Spectrometry; D021962:Membrane Microdomains / Q000201:enzymology; D009154:Mutation; D010168:Palmitates / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000737:chemistry
D016564:Amyloid beta-Protein Precursor; D000924:Anticholesteremic Agents; D010168:Palmitates; D011994:Recombinant Proteins; D002784:Cholesterol; D008148:Lovastatin; D006026:Glycoside Hydrolases; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human