Advanced glycation end-products produced systemically and by macrophages: A common contributor to inflammation and degenerative diseases

Abstract

Advanced glycation end products (AGEs) and their receptor have been implicated in the progressions of many intractable diseases, such as diabetes and atherosclerosis, and are also critical for pathologic changes in chronic degenerative diseases, such as Alzheimer's disease, Parkinson's disease, and alcoholic brain damage. Recently activated macrophages were found to be a source of AGEs, and the most abundant form of AGEs, AGE-albumin excreted by macrophages has been implicated in these diseases and to act through common pathways. AGEs inhibition has been shown to prevent the pathogenesis of AGEs-related diseases in human, and therapeutic advances have resulted in several agents that prevent their adverse effects. Recently, anti-inflammatory molecules that inhibit AGEs have been shown to be good candidates for ameliorating diabetic complications as well as degenerative diseases. This review was undertaken to present, discuss, and clarify current understanding regarding AGEs formation in association with macrophages, different diseases, therapeutic and diagnostic strategy and links with RAGE inhibition.

The Role of Advanced Glycation End Products in Aging and Metabolic Diseases: Bridging Association and Causality

“…Elevated AGE-albumin accumulation from activated microglia has been suggested as potential biomarkers for neurodegenerative diseases (Bayarsaikhan et al, 2016). Activation of macrophages leads to an exacerbated release of AGE-albumin complexes, a major AGE derivative that drives shared pathways resulting in the progression of neurodegeneration (Byun et al, 2017). Upregulation of RAGE-mediated signaling has also been shown in the 6-hydroxydopamine (6-OHDA) induced rat model for neurotoxicity (Serratos et al, 2016).…”

Antiaging effects of bioactive molecules isolated from plants and fungi

“…AGEs are also found in food that are heated or cooked and are readily found in human blood . In animal models, the level of AGEs in the diet correlates with blood AGE levels, and they stimulate inflammation and oxidative stress, leading to the development of diabetes, cardiovascular disease, chronic kidney disease, and neurodegeneration . Some phytochemicals such as proanthocyanidins found in fruits (Table ) and catalpol [ 32 ] found in plants of the Rehmannia genus (Table ) reduce the levels of AGEs in worms and mice, respectively.…”

The link between advanced glycation end products and apoptosis in delayed wound healing

“…As mentioned earlier, when AGEs bind to RAGE, NF‐kB activation occurs leading to cytokine activity. Increased cytokine activity is associated with prolonged inflammation which impacts wound healing negatively; in order for wounds to heal effectively, the inflammatory phase of wound healing needs to cease so that later stages of wound healing may proceed …”