title: Aluminum inhibits proteolytic degradation of amyloid beta peptide by cathepsin D: a potential link between aluminum accumulation and neuritic plaque deposition.
abstract: Neuritic plaques are the key pathological feature of Alzheimer's disease, and amyloid beta (Abeta) peptides are major component of these plaques. In this study, we demonstrated the influence of aluminum (Al) on the Abeta peptide degradation by cathepsin D. Al did not directly affect the cathepsin D activity using small synthetic substrate. However, when Abeta peptides were used as substrate, the apparent inhibitory effect of Al on cathepsin D activity was observed. This inhibitory effect disappeared by treatment of desferrioxamine. These results indicate that Al has the potential to interact and disrupt Abeta peptide catabolism via the inhibition of proteolytic degradation.
authors.affiliation: Department of Environmental Biology, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Hisaka
authors.initials: H
authors.lastname: Saito
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Ishii
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Takahashi
authors.forename: Shinzo
authors.initials: S
authors.lastname: Tanabe
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ogasawara
mesh_terms: D000535:Aluminum / Q000378:metabolism* / Q000494:pharmacology*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D002402:Cathepsin D / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D003676:Deferoxamine / Q000494:pharmacology; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000494:pharmacology; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology*; D011489:Protein Denaturation / Q000187:drug effects; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary / Q000187:drug effects; D015032:Zinc / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D006454:Hemoglobins; D000535:Aluminum; D007501:Iron; D002402:Cathepsin D; D003676:Deferoxamine; D015032:Zinc