Abstract
Nonenzymatic Reactions of Reducing Sugars with Primary Amino Groups of Amino Acids, Proteins, and Nucleic Acids, Followed by Oxidative Degradations Would Lead to the Formation of Advanced Glycation Endproducts (AGEs). the AGEs Exert Multifactorial Effects on Cell Damage Leading to the Onset of Neurological Disorders. the Interaction of AGEs with the Receptors for Advanced Glycation Endproducts (RAGE) Contribute to the Activation of Intracellular Signaling and the Expression of the Pro-Inflammatory Transcription Factors and Various Inflammatory Cytokines. This Inflammatory Signaling Cascade is Associated with Various Neurological Diseases, Including Alzheimer's Disease (AD), Secondary Effects of Traumatic Brain Injury (TBI), Amyotrophic Lateral Sclerosis (ALS), and Diabetic Neuropathy, and Other AGE-Related Diseases, Including Diabetes and Atherosclerosis. Furthermore, the Imbalance of Gut Microbiota and Intestinal Inflammation Are Also Associated with Endothelial Dysfunction, Disrupted Blood–brain Barrier (BBB) and Thereby the Onset and Progression of AD and Other Neurological Diseases. AGEs and RAGE Play an Important Role in Altering the Gut Microbiota Composition and Thereby Increase the Gut Permeability and Affect the Modulation of the Immune-Related Cytokines. the Inhibition of the AGE–RAGE Interactions, through Small Molecule-Based Therapeutics, Prevents the Inflammatory Cascade of Events Associated with AGE–RAGE Interactions, and Thereby Attenuates the Disease Progression. Some of the RAGE Antagonists, Such as Azeliragon, Are Currently in Clinical Development for Treating Neurological Diseases, Including AD, Although Currently There Have Been No FDA-Approved Therapeutics based on the RAGE Antagonists. This Review Outlines the AGE–RAGE Interactions as a Leading Cause of the Onset of Neurological Diseases and the Current Efforts on Developing Therapeutics for Neurological Diseases based on the RAGE Antagonists.
Recommended Citation
V. P. Reddy et al., "RAGE Inhibitors in Neurodegenerative Diseases," Biomedicines, vol. 11, no. 4, article no. 1131, MDPI, Apr 2023.
The definitive version is available at https://doi.org/10.3390/biomedicines11041131
Department(s)
Chemistry
Publication Status
Open Access
Keywords and Phrases
AGEs; Alzheimer's disease; cytokines; glycation; oxidative stress; RAGE; RAGE antagonists; soluble RAGE; traumatic brain injury
International Standard Serial Number (ISSN)
2227-9059
Document Type
Article - Journal
Document Version
Final Version
File Type
text
Language(s)
English
Rights
© 2023 The Authors, All rights reserved.
Creative Commons Licensing
This work is licensed under a Creative Commons Attribution 4.0 License.
Publication Date
01 Apr 2023
