title: The degradation of Abeta(25-35) by the serine protease plasmin is inhibited by aluminium.
abstract: The catabolism of amyloid beta peptides (Abeta) may be important in their accumulation in the brain in both early and late-onset Alzheimer's disease (AD). The serine protease plasmin is one of a suite of proteases implicated in AD. It is a promoter of alpha-cleavage of the amyloid beta precursor protein (AbetaPP) and will degrade Abeta in vitro. Herein we have demonstrated cleavage of the amyloidogenic Abeta(25-35) by plasmin to produce the non-amyloidogenic fragment Abeta(29-35). The activity of plasmin was halved by pre-mixing it with aluminium (Al) prior to its addition to the peptide. An interaction between Al and proteases involved in the catabolism of Abeta might define the putative link between Al and AD.
authors.affiliation: Centre for Science and Technology in Medicine, Keele University, Staffordshire, UK.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Korchazhkina
authors.forename: Alison E
authors.initials: AE
authors.lastname: Ashcroft
authors.forename: Tamas
authors.initials: T
authors.lastname: Kiss
authors.forename: Christopher
authors.initials: C
authors.lastname: Exley
mesh_terms: D000535:Aluminum / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005341:Fibrinolysin / Q000037:antagonists & inhibitors / Q000378:metabolism; D005453:Fluorescence; D006801:Humans; D012697:Serine Endopeptidases / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C439320:amyloid beta-protein (25-36); D000535:Aluminum; D012697:Serine Endopeptidases; D005341:Fibrinolysin