Advanced glycation end product molecules as major culprits behind amyloidogenic protein aggregation

Abstract

Advanced glycation end products (AGEs) are lipids or proteins that are glycated after exposure to sugars. They are commonly seen in the vasculature of diabetics and are thought to have a role in the development of atherosclerosis. AGEs impact diseases like diabetes and neurodegenerative disorders because they are essential in the misfolding and aggregation of proteins. AGE molecules have a significant role in the aggregation of amyloidogenic proteins, which in turn facilitates the production of amyloid formations linked to diseases, including Parkinson's and Alzheimer's. Amyloidogenic proteins and AGEs interact to speed up protein aggregation, which aids in the etiology of neurodegenerative illnesses. Glycation, metal binding, and oxidative stress are some elements that affect the complex interactions that result in the creation of stable fibrillary structures and AGEs, which cause protein aggregation. The impact of AGE-induced protein aggregation on diabetes and neurodegenerative diseases is profound, with AGEs playing a significant role in disease progression. Antioxidants, cross-link breakers, RAGE antagonists, and inhibitors target AGEs and provide ways to reduce the consequences of disease and prevent AGE-induced protein aggregation. In this chapter, we will look at all the statements mentioned above and learn about amyloidogenic protein aggregation and its consequences for disease pathophysiology. © 2026 Elsevier Inc. All rights reserved..