Advanced glycation end products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation

Abstract

The products of nonenzymatic glycation and oxidation of proteins and lipids, the advanced glycation end products (AGEs), accumulate in a wide variety of environments. AGEs may be generated rapidly or over long times stimulated by a range of distinct triggering mechanisms, thereby accounting for their roles in multiple settings and disease states. A critical property of AGEs is their ability to activate receptor for advanced glycation end products (RAGE), a signal transduction receptor of the immunoglobulin superfamily. It is our hypothesis that due to such interaction, AGEs impart a potent impact in tissues, stimulating processes linked to inflammation and its consequences. We hypothesize that AGEs cause perturbation in a diverse group of diseases, such as diabetes, inflammation, neurodegeneration, and aging. Thus, we propose that targeting this pathway may represent a logical step in the prevention/treatment of the sequelae of these disorders.

Serum Fluorescent Advanced Glycation End (F-AGE) products in gestational diabetes patients

“…AGEs may cause tissue injury both directly, through phenomena such as trapping and cross-linking, and indirectly, by binding to specific receptors such as receptors for AGE (RAGE), which is expressed on the surface of numerous cell types, such as macrophages, monocytes, endothelial cells, neurons, and smooth muscle cells (3,4). The AGE-RAGE interaction can lead to oxidative stress, production of growth factors and cytokines, chronic inflammatory responses, and cellular and vascular dysfunction (5,6).…”

“…Elevated AGEs concentrations are associated with several diseases, including diabetes mellitus (DM) (5,7,8). DM is a pathology characterized by hyperglycemia, oxidative stress, inflammation, and consequently, the AGE-RAGE interaction is enhanced (1,5).…”

“…DM is a pathology characterized by hyperglycemia, oxidative stress, inflammation, and consequently, the AGE-RAGE interaction is enhanced (1,5). While some studies have shown that AGE concentrations are higher in type 1 (T1D) and type 2 (T2D) diabetic patients than in healthy subjects, especially in diabetes with secondary complications (9,10), others have shown that AGE concentrations are also elevated in gestational DM (GDM) (11,12), and still other studies have demonstrated that AGEs concentrations were not significantly different between women with GDM and healthy pregnant women (13,14).…”

Association of the glycoxidative stress marker pentosidine with equine laminitis

“…In horses, the level of superoxide dismutase (SOD) (an antioxidant enzyme) in the lamellae is reportedly low (Loftus et al, 2007), which could make the laminar tissues more susceptible to glycoxidative damage. The interactions between AGEs with their specific receptor (RAGE) may be linked to the increased generation of ROS by multiple mechanisms such as by decreasing the activity of SOD and catalase, diminishing glutathione stores, or the activation of protein kinase C (Ramasamy et al, 2005). Glycoxidation may contribute to endothelial dysfunction (Chappey et al, 1997), the cross-linking of collagen and interstitial matrix with reduced turnover and functionality (Avery and Bailey, 2006), the increased release of cytokines that contributes to inflammation and tissue damage (Bengmark, 2007) and to the worsening of insulin resistance (Sandu et al, 2005).…”

Inhibition of non‐enzymatic glycation by silk extracts from a Mexican land race and modern inbred lines of maize (Zea mays)

“…During AGE formation, Amadori rearrangements to more reactive intermediates induce protein cross-linking that not only affects protein function and half-life but also engages signaling cascades transduced by the AGE receptor (RAGE) (Ulrich and Cerami, 2001). AGEs and RAGE activation have been linked to the development of neurological, cardiovascular and renal complications of diabetes and aging (Ramasamy et al, 2005).…”