Fluorescence in probing the biochemical and conformational changes in non-enzymatically glycated proteins

Abstract

Individuals with long-term diabetes often develop micro and macrovascular comorbidities. These complications, driven by persistent high blood sugar, are linked to the biochemical process of glycation reaction. The non-enzymatic glycation (NEG) reaction occurs when reducing sugars or dicarbonyls interact with the positively charged side chains of arginine and lysine amino acids in proteins through nucleophilic addition. As a result of the process advanced glycation end products (AGEs) are generated and accumulated in the tissues, leading to protein misfolding and amyloid formation. Diabetes-related retinopathy, neuropathy, nephropathy, cardiovascular diseases (CVD), and neurodegenerative disorders are among the consequences whose pathogenesis has been linked to glycation. It is crucial to measure NEG to understand and control the threat they pose to the body. Fluorescence-based detection methods have evolved into a valuable tool for investigating the intricate mechanisms underlying protein glycation, offering high sensitivity and specificity in detecting structural alterations associated with this process. In this comprehensive review, we discuss the NEG of proteins, their pathophysiological effects, and the methods for detection, highlighting fluorescence-based techniques. This review underscores the significance of fluorescence as a versatile tool for unraveling the multifaceted aspects of NEG and its implications in health and disease.