Influence of advanced glycation end-products and AGE-inhibitors on nucleation-dependent polymerization of β-amyloid peptide

Gerald Münch, Samantha Mayer, Jürgen Michaelis, Alan R. Hipkiss, Peter Riederer, Renate Müller, Arne Neumann, Reinhard Schinzel, Anne M. Cunningham

Research output: Contribution to journalArticlepeer-review

185 Citations (Scopus)

Abstract

Nucleation-dependent polymerization of P-amyloid peptide, the major component of plaques in patients with Alzheimer's disease, is significantly accelerated by crosslinking through Advanced Glycation End-products (AGEs) in vitro. During the polymerization process, both nucleus formation and aggregate growth are accelerated by AGE-mediated crosslinking. Formation of the AGE crosslinked amyloid peptide aggregates could be attenuated by the AGE-inhibitors Tenilsetam, aminoguanidine and carnosine. These experimental data, and clinical studies, reporting a marked improvement in cognition and memory in Alzheimer's disease patients after Tenilsetam treatment, suggest that AGEs might play an important role in the etiology or progression of the disease. Thus AGE-inhibitors may generally become a promising drug class for the treatment of Alzheimer's disease.

Original languageEnglish
Pages (from-to)17-29
Number of pages13
JournalBiochimica et Biophysica Acta. Molecular Basis of Disease
Volume1360
Issue number1
DOIs
Publication statusPublished - 27 Feb 1997
Externally publishedYes

Keywords

  • β-Amyloid peptide
  • Advanced glycation end-product
  • AGE-inhibitor
  • Alzheimer's disease

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