Understanding the Role of Protein Glycation in the Amyloid Aggregation Process

Abstract

Protein function and flexibility is directly related to the native distribution of its structural elements and any alteration in protein architecture leads to several abnormalities and accumulation of misfolded proteins. This phenomenon is associated with a range of increasingly common human disorders, including Alzheimer and Parkinson diseases, type II diabetes, and a number of systemic amyloidosis characterized by the accumulation of amyloid aggregates both in the extracellular space of tissues and as intracellular deposits. Post-translational modifications are known to have an active role in the in vivo amyloid aggregation as able to affect protein structure and dynamics. Among them, a key role seems to be played by non-enzymatic glycation, the most unwanted irreversible modification of the protein structure, which strongly affects long-living proteins throughout the body. This study provided an overview of the molecular effects induced by glycation on the amyloid aggregation process of several protein models associated with misfolding diseases. In particular, we analyzed the role of glycation on protein folding, kinetics of amyloid formation, and amyloid cytotoxicity in order to shed light on the role of this post-translational modification in the in vivo amyloid aggregation process.

Hallmarks of Metabolic Reprogramming and Their Role in Viral Pathogenesis

“…Non-crosslinking AGEs are AGEs that bind to lysine or arginine residues and create protein adducts. Crosslinking AGEs have been shown to affect protein structure and function and result in reduced enzymatic activity, protein aggregation, altered biophysical properties, and changes in protein–protein interactions [ 265 , 266 , 267 , 268 ]. Non-crosslinking AGEs have been shown to change receptor ligands, block receptors, block protein cleavage sites, cause misfolding of protein, and inhibit protein degradation [ 240 , 264 , 269 , 270 , 271 ].…”

Biophysical, Biochemical, and Molecular Docking Investigations of Anti-Glycating, Antioxidant, and Protein Structural Stability Potential of Garlic

“…AGEs are a complex and highly reactive group of heterogeneous compounds produced by glycation of proteins by reducing sugars [ 1 , 2 ]. Protein glycation has been shown to increase the accumulation of AGEs, the production and release of reactive oxygen species (ROS), and the structural and functional alteration of proteins, as well as resulting in tissue damage [ 3 , 4 ]. AGEs interact with particular receptors or bind proteins, activating a number of signaling pathways implicated in diabetic complications such as nephropathy, cataracts, Alzheimer’s disease, and atherosclerosis, among others [ 5 , 6 ].…”

Behavior of Regular Insulin in a Parenteral Nutrition Admixture: Validation of an LC/MS-MS Assay and the In Vitro Evaluation of Insulin Glycation

“…Given that PN contains high amounts of dextrose, glycation via a Maillard reaction might be involved in the loss of insulin, as has been described by Fry et al for amino acids [ 26 ]. This phenomenon has been extensively described in vitro and in vivo for proteins in general [ 27 , 28 , 29 ] and for insulin in particular [ 30 , 31 , 32 , 33 , 34 , 35 ]. Most of the latter studies characterized the glycation products under “forced” conditions (i.e., high-temperature incubation for a long period of time) and/or reducing conditions.…”