Beta-sheet breaker peptides inhibit fibrillogenesis in a rat brain model of amyloidosis: implications for Alzheimer's therapy

Nat Med. 1998 Jul;4(7):822-6. doi: 10.1038/nm0798-822.


Inhibition of cerebral amyloid beta-protein deposition seems to be an important target for Alzheimer's disease therapy. Amyloidogenesis could be inhibited by short synthetic peptides designed as beta-sheet breakers. Here we demonstrate a 5-residue peptide that inhibits amyloid beta-protein fibrillogenesis, disassembles preformed fibrils in vitro and prevents neuronal death induced by fibrils in cell culture. In addition, the beta-sheet breaker peptide significantly reduces amyloid beta-protein deposition in vivo and completely blocks the formation of amyloid fibrils in a rat brain model of amyloidosis. These findings may provide the basis for a new therapeutic approach to prevent amyloidosis in Alzheimer's disease.

Publication types

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

MeSH terms

  • Alzheimer Disease / therapy*
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Peptides / pharmacology
  • Amyloid beta-Peptides / toxicity
  • Amyloidosis / prevention & control*
  • Animals
  • Brain / metabolism*
  • Disease Models, Animal
  • Humans
  • Male
  • Peptide Fragments / metabolism*
  • Peptide Fragments / pharmacology
  • Peptide Fragments / toxicity
  • Peptides / pharmacology*
  • Rats
  • Rats, Inbred F344
  • Tumor Cells, Cultured


  • Amyloid beta-Peptides
  • Peptide Fragments
  • Peptides
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)