What is the role of advanced glycation end products (AGEs) in the etiology of beta-2-microglobulin (beta-2m) amyloidosis?

Updated: Nov 14, 2019
  • Author: Anita Basu, MD, FACP; Chief Editor: Vecihi Batuman, MD, FASN  more...
  • Print

Following the identification of advanced glycation end products (AGEs) in beta-2m amyloid deposits, the role of AGE has been the focus of much research. [6]

AGEs make up a heterogeneous group of compounds formed by nonenzymatic glycation and oxidative reactions between reducing sugars, lipids, and protein amino groups.

HD and peritoneal dialysis are ineffective in removing these low–molecular weight compounds from circulation.

As AGE-modified beta-2m accumulates, chemotaxis is enhanced, stimulating macrophages to release proinflammatory cytokines, as well as interfering with collagen synthesis. It has been suggested that the interaction of AGE-modified beta-2m with mononuclear phagocytes (MPs), cells important in the pathogenesis of the inflammatory arthropathy of DRA, is mediated by the receptor for AGEs, or RAGE.

RAGEs are central binding sites for AGEs formed in vivo. [7] AGE beta-2m/MP/RAGE interaction likely contributes to the initiation of an inflammatory response in amyloid deposits of patients on long-term HD. This inflammatory response may ultimately lead to bone and joint destruction.

Oxidation of beta-2m may enhance amyloid deposition. Studies suggest that increased oxidative stress during HD and exposure of beta-2m to hydroxyl radicals stimulate the autoxidation of unstable molecules, leading to augmented AGE production.

Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!