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

Abstract	Nucleation-dependent polymerization of beta-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.
Authors	G Münch, S Mayer, J Michaelis, A R Hipkiss, P Riederer, R Müller, A Neumann, R Schinzel, A M Cunningham
Journal	Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1360 Issue 1 Pg. 17-29 (Feb 27 1997) ISSN: 0006-3002 [Print] Netherlands
PMID	9061036 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Amyloid beta-Peptides Benzothiazoles Cross-Linking Reagents Glycation End Products, Advanced Guanidines Neuropeptide Y Peptide Fragments Piperazines Thiazoles Thiophenes amyloid beta-protein (1-40) thioflavin T Fructose Carnosine tenilsetam pimagedine
Topics	Alzheimer Disease (drug therapy, metabolism, pathology) Amyloid beta-Peptides (metabolism) Benzothiazoles Carnosine (pharmacology) Cognition (drug effects) Cross-Linking Reagents (pharmacology) Fructose (pharmacology) Glycation End Products, Advanced (antagonists & inhibitors, pharmacology) Guanidines (pharmacology) Humans Memory (drug effects) Neuropeptide Y (metabolism) Particle Size Peptide Fragments (metabolism) Piperazines (pharmacology, therapeutic use) Protein Structure, Secondary Solubility Temperature Thiazoles (metabolism) Thiophenes (pharmacology, therapeutic use)

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