ReviewA review on prevention of glycation of proteins: Potential therapeutic substances to mitigate the severity of diabetes complications
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Glycation of proteins: The Maillard reaction
Louis-Camille Maillard, a French scientist, in 1912, described the formation of yellow-brown coloration upon heating reducing sugars with amino acids [1]. The series of complex reactions involved in the browning was termed as Maillard reaction. As summarized by Hodge in 1953, the primary interest of the research associated with the Maillard reaction during that period was limited to the coloring and flavoring of the food when kept for a longer period of time [2]. Over the past few decades,
Advanced glycation end products (AGEs)
AGEs are complex, heterogeneous adducts generated during the course of glycation and are mostly characterized by their brown color and fluorescence characteristics. Many AGEs have been identified and characterized over the years in both in vivo and in vitro conditions; still, the chemistry associated with these are not clearly understood. Nε-carboxymethyl lysine (CML) was the first AGE isolated from glycated protein in vivo. It is derived from the lysine residues and has been detected in skin
Glycation and aggregation of proteins
Alzheimer's disease, amyotrophic lateral sclerosis, prion diseases and Parkinson's disease are crippling diseases that need extensive study. Protein misfolding, aggregation and precipitation all appear to be linked to neurotoxicity in these diseases [90], [91]. The physiological changes are linked to the development of fibrillar aggregates known as amyloid fibrils, which typically develop in the extracellular region or as intracellular deposits [92], [93]. Aggregation events are directly
Inhibition of glycation
In diabetic patients, glycation and the aggregation of AGEs are significant contributors to diabetes and related pathogenesis. As a result, finding effective antiglycating agents and preventing the development of intermediate or end products may be a useful and beneficial approach in the management of chronic complications. Anti-glycation biochemical pathways, in general, involve some mechanisms that may slow or suppress the glycation phase in vivo, thus inhibiting the formation of AGEs. Below
Inhibitors of glycation and AGE formation
Antiglycating agents may obstruct glycation and AGE development by interfering with various possible locations. Some could be able to compete for the protein's amino groups and others may attach directly to the protein or the glycation intermediates to halt the progression to AGE forming. Otherwise, they could have the ability to replace glycating sugars in the open-chain shape. A number of potential AGE inhibitors have also been suggested. Several inhibitors have been developed, and several
Natural and synthetic inhibitors: current shortcomings and potential prospects
Synthetic medicines are sometimes linked to drawbacks such as high expense, hypoglycemia, stomach disturbances, liver toxicity, exhaustion, fatigue, shortness of breath, vomiting, blurred vision, lactic acidosis, and kidney toxicity, to name a few. Such synthetic medications are not permitted to be taken by some renal patients. On the other hand, lack of dose-dependent standardization of inhibitors for effectiveness and protection, poor bioavailability, and weak aqueous solubility are some of
Conclusion
Increased AGE generation and occurrence have been linked to the development of diabetic complications and other pathologies. AGE levels are exceptionally high in people with diabetes, according to clinical research and experimental studies, and high blood sugar speeds up protein glycation and facilitates AGE development. Understanding the impact of diabetes in today's world and the wide variety of diabetes complications, medications to mitigate diabetes complications are urgently needed. The
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
ASR is highly grateful to the CSIR, Gov't of India, for financial support [File No. 01(2903)/17/EMR-II]. SS thanks TEQIP-III, NIT Meghalaya for his research fellowship.
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