Influence of advanced glycation end-products and AGE-inhibitors on nucleation-dependent polymerization of beta-amyloid peptide.
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.
Münch
G
G
Theodor-Boveri-Institute (Biocenter), Würzburg, Germany. muench@biozentrum.uni-wuerzburg.de
Mayer
S
S
Michaelis
J
J
Hipkiss
A R
AR
Riederer
P
P
Müller
R
R
Neumann
A
A
Schinzel
R
R
Cunningham
A M
AM
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D052160:Benzothiazoles; D002336:Carnosine / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000494:pharmacology; D005632:Fructose / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D008568:Memory / Q000187:drug effects; D009478:Neuropeptide Y / Q000378:metabolism; D010316:Particle Size; D010446:Peptide Fragments / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D017433:Protein Structure, Secondary; D012995:Solubility; D013696:Temperature; D013844:Thiazoles / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology* / Q000627:therapeutic use
D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D003432:Cross-Linking Reagents; D017127:Glycation End Products, Advanced; D006146:Guanidines; D009478:Neuropeptide Y; D010446:Peptide Fragments; D010879:Piperazines; D013844:Thiazoles; D013876:Thiophenes; C078592:amyloid beta-protein (1-40); C009462:thioflavin T; D005632:Fructose; D002336:Carnosine; C059511:tenilsetam; C004479:pimagedine