Selection of peptides binding to the amyloid b-protein reveals potential inhibitors of amyloid formation.

Published

Journal Article

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by extracellular amyloid plaques, cerebrovascular amyloid deposits, intracellular neurofibrillary tangles, and neuronal loss. Amyloid deposits are composed of insoluble fibers of a 39-43 amino acid peptide named the amyloid beta-protein (A beta). Neuropathological and genetic studies provide strong evidence of a key role for A beta amyloidosis in the pathogenesis of AD. Therefore, an obvious pharmacological target for treatment of AD is the inhibition of amyloid growth and/or inhibition of amyloid function. We took an unbiased approach to generate new inhibitors of amyloid formation by screening a FliTrx combinatorial peptide library for A beta binding peptides and identified four groups of peptides with different A beta binding motifs. In addition, we designed and examined peptides mimicking the A beta binding domain of transthyretin (TTR). Our results showed that A beta binding peptides selected from FliTrx peptide library and from TTR-peptide analogs are capable of inhibiting A beta aggregation and A beta deposition in vitro. These properties demonstrate that binding of selected peptides to the amyloid beta-protein may provide potent therapeutic compounds for the treatment AD.

Full Text

Duke Authors

Cited Authors

  • Schwarzman, AL; Tsiper, M; Gregori, L; Goldgaber, D; Frakowiak, J; Mazur-Kolecka, B; Taraskina, A; Pchelina, S; Vitek, MP

Published Date

  • December 2005

Published In

Volume / Issue

  • 12 / 4

Start / End Page

  • 199 - 209

PubMed ID

  • 16399644

Pubmed Central ID

  • 16399644

International Standard Serial Number (ISSN)

  • 1350-6129

Digital Object Identifier (DOI)

  • 10.1080/13506120500350762

Language

  • eng

Conference Location

  • England