Non-chaperone proteins can inhibit aggregation and cytotoxicity of Alzheimer amyloid ß peptide

Abstract

Many factors are known to influence the oligomerization, fibrillation, and amyloid formation of the Aß peptide that is associated with Alzheimer disease. Other proteins that are present when Aß peptides deposit in vivo are likely to have an effect on these aggregation processes. To separate specific versus broad spectrum effects of proteins on Aß aggregation, we tested a series of proteins not reported to have chaperone activity: catalase, pyruvate kinase, albumin, lysozyme, α-lactalbumin, and ß-lactoglobulin. All tested proteins suppressed the fibrillation of Alzheimer Aß(1-40) peptide at substoichiometric ratios, albeit some more effectively than others. All proteins bound non-specifically to Aß, stabilized its random coils, and reduced its cytotoxicity. Surprisingly, pyruvate kinase and catalase were at least as effective as known chaperones in inhibiting Aß aggregation. We propose general mechanisms for the broad-spectrum inhibition Aß fibrillation by proteins. The mechanisms we discuss are significant for prognostics and perhaps even for prevention and treatment of Alzheimer disease.