Copper and zinc binding modulates the aggregation and neurotoxic properties of the prion peptide PrP106-126

Abstract

The abnormal form of the prion protein (PrP) is believed to be responsible for the transmissible spongiform encephalopathies. A peptide encompassing residues 106-126 of human PrP (PrP106-126) is neurotoxic in vitro due its adoption of an amyloidogenic fibril structure. The Alzheimer's disease amyloid β peptide (Aβ) also undergoes fibrillogenesis to become neurotoxic. Aβ aggregation and toxicity is highly sensitive to copper, zinc, or iron ions. We show that PrP106-126 aggregation, as assessed by turbidometry, is abolished in Chelex-100-treated buffer. ICP-MS analysis showed that the Chelex-100 treatment had reduced Cu2+ and Zn2+ levels approximately 3-fold. Restoring Cu2+ and Zn2+ to their o..