Zn-dependent β-amyloid Aggregation and its Reversal by the Tetrapeptide HAEE.

ABSTRACT: The pathogenesis of Alzheimer's disease (AD) is associated with the formation of cerebral amyloid plaques, the main components of which are the modified Aβ molecules as well as the metal ions. Aβ isomerized at Asp7 residue (isoD7-Aβ) is the most abundant isoform in amyloid plaques. We hypothesized that the pathogenic effect of isoD7-Aβ is due to the formation of zinc-dependent oligomers, and that this interaction can be disrupted by the rationally designed tetrapeptide (HAEE). Here, we utilized surface plasmon resonance, nuclear magnetic resonance, and molecular dynamics simulation to demonstrate Zn²⁺-dependent oligomerization of isoD7-Aβ and the formation of a stable isoD7-Aβ:Zn²⁺:HAEE complex incapable of forming oligomers. To demonstrate the physiological importanc

SUBMITTER: Mitkevich VA 

PROVIDER: S-EPMC10017155 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature