A mimotope of Aβ oligomers may also behave as a β-sheet inhibitor

FEBS Lett. 2017 Nov;591(21):3615-3624. doi: 10.1002/1873-3468.12871. Epub 2017 Oct 13.

Abstract

Beta-amyloid (Aβ) oligomers are strongly associated with the cascade of harmful events leading to neurodegeneration in Alzheimer's disease (AD). Elimination of Aβ oligomers or inhibition of Aβ assembly is a valuable therapeutic approach for the treatment of AD. Here, we obtained a mimotope of Aβ oligomers, AOEP2, by screening a peptide library using oligomer-specific antibodies. The antibodies induced by AOEP2 specifically recognize Aβ oligomers rather than monomers and fibrils. Interestingly, the AOEP2 peptide binds to Aβ monomers and inhibits the formation of Aβ oligomers and β-sheet structure, reduces Aβ42-induced neurotoxicity, and decreases the release of proinflammatory cytokines. Taken together, AOEP2, a novel multifunctional peptide directly or indirectly targeting Aβ, has promising therapeutic potential for AD.

Keywords: aggregation; beta-amyloid oligomer; mimotope; peptide; vaccine.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Peptide Fragments / chemistry*
  • Peptide Fragments / metabolism
  • Peptide Library*
  • Protein Multimerization*
  • Protein Structure, Secondary

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • Peptide Library
  • amyloid beta-protein (1-42)