Effects of zinc and carnosine on aggregation kinetics of Amyloid-β40 peptide.

The accumulation and amyloid formation of amyloid-β (Aβ) peptides is closely associated with the pathology of Alzheimer's disease. The physiological environment wherein Aβ aggregation happens is crowded with a large variety of metal ions including Zn. In this study, we investigated the role of Zn in regulating the aggregation kinetics of Aβ40 peptide. Our results show that Zn can shift a typical single sigmoidal aggregation kinetics of Aβ40 to a biphasic aggregation process. Zn aids in initiating the rapid self-assembly of monomers to form oligomeric intermediates, which further grow into amyloid fibrils in the first aggregation phase. The presence of Zn also retards the appearance of the second aggregation phase in a concentration dependent manner. In addition, our results show that a natural dipeptide, carnosine, can greatly alleviate the effect of Zn on Aβ aggregation kinetics, most likely by coordinating with the metal ion to form chelates. These results suggest a potential in vivo protective effect of carnosine against the cytotoxicity of Aβ by suppressing Zn-induced rapid formation of Aβ oligomers.