Title:Advanced Glycation End Products: Association with the Pathogenesis of Diseases and the Current Therapeutic Advances
VOLUME: 11 ISSUE: 2
Author(s):Thekkuttuparambil A. Ajith and Puzhikunathu Vinodkumar
Affiliation:Department of Biochemistry, Amala Institute of Medical Sciences, Amala Nagar, Thrissur-680 555, Kerala, India.
Keywords:Advanced glycation end products, dicarbonyls, cytokines, reactive oxygen species, aminoguanidine, resveratrol, curcumin.
Abstract:Advanced glycation end products (AGE) such as N-ε-carboxy-ethyl-lysine
(CEL), N-ε-carboxy-methyl-lysine (CML), imidazolone, methyl-glyoxal-lysine dimer
(MOLD), glyoxal-lysine dimer (GOLD), pyrraline and pentosidine have been
imparted in the development and worsening of complications of diabetes. They are also
involved in atherosclerosis, normal aging process, arthritis, cancer and progression of
age-related neurodegenerative diseases like Alzheimer's disease. Endogenously, they
are formed by nonenzymatic glycation by aldoses/ketoses to form intermediate
precursor that were slowly converted into AGE. A positive correlation was observed
with the level of AGEs formation and progression of the diseases. Exogenously, they
formed in foods when they were cooked at very high temperature. AGEs can interact
with the cell surface receptors of AGE (RAGE) to release cytokines, free radicals as well as directly modify
the extracellular matrix and action of hormones. Hence, the mechanism of AGE association with
pathogenesis of diseases can be ascribed mainly to the generated cytokines and free radicals. Second type of
receptors such as AGE receptor-1, 2 and 3 were more specific and involved in their detoxification and
clearance. Therapeutic agents were used to inhibit AGEs formation, traps the reactive carbonyl intermediate
precursors, interfering with Amadori's products, cross-link breaker and low molecular weight inhibitors of
RAGE had been described as well. Despite the several therapeutic agents described so far, none of
them have proven to be recommended for clinical use. Furthermore, no methods or standard units
were accepted universally to measure AGEs are existing. This review discusses AGEs formation,
association with diseases and therapeutic agents to alleviate them.
