Non-chaperone Proteins Can Inhibit Aggregation and Cytotoxicity of Alzheimer Amyloid beta Peptide

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