Therapeutic potential of AGE inhibitors and breakers of AGE protein cross-links

Expert Opin Investig Drugs. 2001 Nov;10(11):1977-87. doi: 10.1517/13543784.10.11.1977.

Abstract

Glucose and other reducing sugars react non-enzymatically with proteins leading to the formation of advanced glycosylation end products (AGEs) and AGE-derived protein cross-linking. Formation of AGEs is a normal physiological process, which is accelerated under the hyperglycaemic condition in diabetes. Under normal conditions, AGEs build up slowly and accumulate as one ages. Numerous studies have indicated that AGEs contribute to the pathological events leading to diabetic complications, such as age-related diseases, including nephropathy, retinopathy, vasculopathy and neuropathy. Potential therapeutic approaches to prevent these complications include pharmacological inhibition of AGE formation and disruption of pre-formed AGE-protein cross-links. Studies using animal models and preliminary clinical trials have shown the ability of the AGE-inhibitor, pimagedine and the cross-link breaker, ALT-711, to reduce the severity of pathologies of advanced glycosylation. These agents offer potential treatments for glucose-derived complications of diabetes and ageing.

Publication types

  • Review

MeSH terms

  • Animals
  • Clinical Trials as Topic
  • Cross-Linking Reagents
  • Diabetes Complications
  • Diabetes Mellitus / metabolism
  • Glycation End Products, Advanced / antagonists & inhibitors*
  • Glycation End Products, Advanced / chemistry*
  • Glycation End Products, Advanced / physiology
  • Humans

Substances

  • Cross-Linking Reagents
  • Glycation End Products, Advanced