Protein Glycation: An Old Villain is Shedding Secrets

Abstract

: The glycation of proteins is 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 widespread 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.

Novel Properties of Old Propranolol─Assessment of Antiglycation Activity through In Vitro and In Silico Approaches

“…The unstable Schiff base may be transformed into more stable APs that will later undergo dehydration and rearrangement with AGE formation. Extended exposure of proteins to Glc and other sugars results in the α-helix transition into a linear structure, activating the formation of βA. − …”

Antiglycoxidative properties of amantadine – a systematic review and comprehensive in vitro study

“…The Schiff base can be converted into more stable AP which undergo dehydration and rearrangement accompanied by the formation of AGE, such as N ϵ -carboxymethyl-lysine (CML) and N ϵ -carboxyethyl-lysine (CEL). Prolonged exposure of proteins to Glc and other sugars causes the α-helix transition to a linear structure, triggering the formation of βA 82–84 .…”

“…In the present study, we used various glycation (Glc, Fru, Gal, GO, and MGO) and oxidation (ChT) factors to determine the impact of amantadine on glycoxidation, glycation, and oxidation protein products. Glycation is a non-enzymatic reaction that occurs between the carbonyl group of reducing sugars and proteins with high levels of free amino groups 82 . We showed that the content of glycoxidation products was significantly higher in BSA samples with the addition of all glycation agents compared to BSA without additives (except TRY).…”

Agomelatine's antiglycoxidative action—In vitro and in silico research and systematic literature review

“…Protein glycation is the process of non-enzymatic reaction of reducing substances (sugars, aldehydes, and/or ketones) with free amino groups of proteins ( 43 ). Protein glycation proceeds in multiple steps (collectively called a Maillard reaction) and begins with the reaction of carbonyl groups of glycation agents with proteins rich in free amino groups.…”