Protective effect of zinc on amyloid-β 25-35 and 1-40 mediated toxicity

Amyloid P-peptide (A beta) is widely held to be associated with Alzheimer's disease, the insoluble aggregates of the peptide being the major constituents of senile plaques. In this study, we evaluated the effect of Zn2+ (5, 50 and 200 mu M) on A beta induced toxicity using the human teratocarcinome (NT2) cell line. Our results proved that 50 and 200 mu M Zn2+ protected NT2 cells from AP 25-35 toxicity. Zinc was also shown to be effective by preventing the loss of mitochondrial membrane potential (Delta Psi(m)) induced by AP 25-35, not allowing cytochrome c release from mitochondria, and subsequently, caspase 3 activation. However, when the cells were treated with A beta 1-40, only 5 mu M Zn2+ had a protective effect. We have further observed that 5 mu M Zn2+ prevented A beta 1-40 aggregation into a P-sheet structure. Considering the results presented, we argue that Zn2+ has a concentration-dependent protective effect.