title: Non-chaperone proteins can inhibit aggregation and cytotoxicity of Alzheimer amyloid β peptide.
abstract: Many factors are known to influence the oligomerization, fibrillation, and amyloid formation of the Aβ peptide that is associated with Alzheimer disease. Other proteins that are present when Aβ peptides deposit in vivo are likely to have an effect on these aggregation processes. To separate specific versus broad spectrum effects of proteins on Aβ aggregation, we tested a series of proteins not reported to have chaperone activity: catalase, pyruvate kinase, albumin, lysozyme, α-lactalbumin, and β-lactoglobulin. All tested proteins suppressed the fibrillation of Alzheimer Aβ(1-40) peptide at substoichiometric ratios, albeit some more effectively than others. All proteins bound non-specifically to Aβ, stabilized its random coils, and reduced its cytotoxicity. Surprisingly, pyruvate kinase and catalase were at least as effective as known chaperones in inhibiting Aβ aggregation. We propose general mechanisms for the broad-spectrum inhibition Aβ fibrillation by proteins. The mechanisms we discuss are significant for prognostics and perhaps even for prevention and treatment of Alzheimer disease.
authors.affiliation: From the Gorlaeus Laboratory, Leiden Institute of Chemistry, Leiden University, 2300RA Leiden, The Netherlands and.
authors.forename: Jinghui
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Biochemistry and Biophysics, Stockholm University SE-10691 Stockholm, Sweden.
authors.forename: Sebastian K T S
authors.initials: SK
authors.lastname: Wärmländer
authors.affiliation: Department of Biochemistry and Biophysics, Stockholm University SE-10691 Stockholm, Sweden.
authors.forename: Astrid
authors.initials: A
authors.lastname: Gräslund
authors.affiliation: From the Gorlaeus Laboratory, Leiden Institute of Chemistry, Leiden University, 2300RA Leiden, The Netherlands and Abrahams@chem.leidenuniv.nl.
authors.forename: Jan Pieter
authors.initials: JP
authors.lastname: Abrahams
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity*; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism*; D066329:Protein Aggregates; D066263:Protein Aggregation, Pathological
chemical_list: D016229:Amyloid beta-Peptides; D018832:Molecular Chaperones; D066329:Protein Aggregates
keywords: Aggregates; Alzheimer Disease; Amyloid-β (AB); Fibrillation; Protein Aggregation; Protein-Protein Interaction; Spectroscopy; Toxicity
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