Protein Glycation: An Old Villain is Shedding Secrets

Abstract

The glycation of proteins is a non-physiological post-translational incorporation of carbohydrates onto the free amines or guanidines of proteins and some lipids. Although the existence of glycated proteins has been known for forty years, a full understanding of their pathogenic nature has been slow in accruing. In recent years, however, glycation has gained wide-spread acceptance as a contributing factor in numerous metabolic, autoimmune and neurological disorders, tying together several confounding aspects of disease etiology. From diabetes, arthritis and lupus, to multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's and Parkinson's diseases, an emerging glycation / inflammation paradigm now offers significant new insight into a physiologically important toxicological phenomenon. It exposes novel drug targets and treatment options, and may even lay foundations for long-awaited breakthroughs. This 'current frontier' article briefly profiles current knowledge regarding the underlying causes of glycation, the structural biology implications of such modifications and their pathological consequences. Although several emerging therapeutic strategies for addressing glycation pathologies are introduced, the primary purpose of this mini-review is to raise awareness of the challenges and opportunities inherent in this emerging new medicinal target area.