The AGE of the matrix: Chemistry, consequence and cure
article
Accumulation of advanced glycation endproducts (AGEs) plays a crucial part in the development of age-related diseases and diabetic complications. AGEs are formed in vivo via the so-called Maillard reaction: a reducing sugar reacts with a protein to form a labile Amadori product that is subsequently stabilized, producing an irreversible, non-enzymatic post-translational modification of the protein involved. Recently, it has become clear that, in addition to sugars, lipids play an important role in the initiation of AGE formation, and that genetic factors contribute to an individual's AGE levels. The highest AGE levels are found in tissues with slow turnover, such as tendon, skin, bone, amyloid plaques and cartilage. AGEs exert their effects by adversely affecting the mechanical properties of the matrix and by modulating tissue turnover. In cartilage, these detrimental effects result in tissue that is more prone to the development of osteoarthritis. As such, the accumulation of AGEs provides the first molecular mechanism explaining the age-related increase in the incidence of osteoarthritis. Ongoing research into anti-AGE-ing therapies, such as pyrodoxamine and thiazolium compounds, which are often developed to prevent AGE-induced diabetic complications, might also prove beneficial for the prevention of osteoarthritis. © Elsevier Ltd. All rights reserved. Chemicals / CAS: advanced glycation end product receptor, 198785-73-8, 247590-69-8; alagebrium, 341028-37-3; glucosamine, 3416-24-8, 4607-22-1; lipid, 66455-18-3; pyridoxamine, 13876-70-5, 5103-96-8, 524-36-7, 85-87-0; Glycosylation End Products, Advanced
Topics
advanced glycation end productadvanced glycation end product receptoralagebriumantidiabetic agentbiological markerglucosaminelipidlipoproteinn phenacyl 4,5 dimethylthiazoliumn phenacylthiazoliumpyridoxaminesoluble advanced glycation end product receptorsugarunclassified drugAmadori rearrangementbonediabetes mellitusglycationheredityhumanin vivo studymolecular mechanicsnonhumanosteoarthritispathophysiologypriority journalprotein modificationprotein processingprotein stabilityratskintendontissue distributionAgingAnimalsGlycosylation End Products, AdvancedHumansOsteoarthritis
TNO Identifier
237794
ISSN
14714892
Source
Current Opinion in Pharmacology, 4(3), pp. 301-305.
Pages
301-305
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