Advanced glycation end products (AGEs), formed through the nonenzymatic reaction of reducing sugars with the side-chain amino groups of lysine or arginine of proteins, followed by further glycoxidation reactions under oxidative stress conditions, are involved in the onset and exacerbation of a variety of diseases, including diabetes, atherosclerosis, and Alzheimer's disease (AD) as well as in the secondary stages of traumatic brain injury (TBI). AGEs, in the form of intra- and interprotein crosslinks, deactivate various enzymes, exacerbating disease progression. The interactions of AGEs with the receptors for the AGEs (RAGE) also result in further downstream inflammatory cascade events. The overexpression of RAGE and the AGE-RAGE interactions are especially involved in cases of Alzheimer's disease and other neurodegenerative diseases, including TBI and amyotrophic lateral sclerosis (ALS). Maillard reactions are also observed in the gut bacterial species. The protein aggregates found in the bacterial species resemble those of AD and Parkinson's disease (PD), and AGE inhibitors increase the life span of the bacteria. Dietary AGEs alter the gut microbiota composition and elevate plasma glycosylation, thereby leading to systemic proinflammatory effects and endothelial dysfunction. There is emerging interest in developing AGE inhibitor and AGE breaker compounds to treat AGE-mediated pathologies, including diabetes and neurodegenerative diseases. Gut-microbiota-derived enzymes may also function as AGE-breaker biocatalysts. Thus, AGEs have a prominent role in the pathogenesis of various diseases, and the AGE inhibitor and AGE breaker approach may lead to novel therapeutic candidates.
V. P. Reddy et al., "Advanced Glycation End Products in Health and Disease," Microorganisms, vol. 10, no. 9, article no. 1848, MDPI, Sep 2022.
The definitive version is available at https://doi.org/10.3390/microorganisms10091848
Keywords and Phrases
advanced glycation end products; AGE breakers; AGE inhibitors; Alzheimer's disease; aminoguanidine; diabetes; Maillard reaction; polyphenols; receptors for AGEs; traumatic brain injury
International Standard Serial Number (ISSN)
Article - Journal
© 2023 The Authors, All rights reserved.
Creative Commons Licensing
This work is licensed under a Creative Commons Attribution 4.0 License.
01 Sep 2022