The advanced stage of the glycation process (one of the post-translational modifications of
proteins) leads to the formation of
advanced glycation end-products (AGEs) and plays an important role in the pathogenesis of angiopathy in diabetic patients, in aging, and in
neurodegenerative diseases. However, it is still not clear which AGEs subtypes play a pathogenetic role and which of several AGEs receptor mediate AGEs effects on cells. We have provided direct immunochemical evidence for the existence of six distinct AGEs structures (AGEs-1 to -6) within the AGEs-modified
proteins and
peptides that circulate in the serum of diabetic patients. Recently we demonstrated for the first time that
glyceraldehyde-derived AGEs (AGEs-2) and
glycolaldehyde-derived AGEs (AGE-3) have diverse
biological activities on vascular wall cells, mesangial cells, Schwann cells,
malignant melanoma cells and cortical neurons. We also demonstrated for the first time that
acetaldehyde (AA)-derived AGEs (AA-AGE) have cytotoxic activity on cortical neurons and the AA-AGE
epitope was detected in human brain of alcoholics. These results indicate that of the various types of AGEs structures that can form in vivo, the toxic AGEs (TAGE) structures (AGEs 2, 3, and AA-AGE), but not non-toxic AGEs (N-
carboxymethyllysine,
pentosidine,
pyrraline etc.) are likely to play an important role in the pathophysiological processes associated with AGEs formation.