Non-chaperone Proteins Can Inhibit Aggregation and Cytotoxicity of Alzheimer Amyloid {beta} Peptide [Molecular Bases of Disease]

August 6th, 2014 by Luo, J., Warmlander, S. K. T. S., Graslund, A., Abrahams, J. P.

Many factors are known to influence the oligomerisation, fibrillation and amyloid formation of the Aβ peptide that is associated with Alzheimer′s Disease. Other proteins that are present when Aβ peptides deposit in vivo, are likely to have an effect on these aggregation processes. In order to separate specific vs. 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′s Aβ(1-40) peptide at sub-stoichiometric ratios, albeit some more effectively than others. All proteins bound non-specifically to Aβ, stabilised 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′s Disease.