https://scholars.lib.ntu.edu.tw/handle/123456789/632649
標題: | The Development of Maillard Reaction, and Advanced Glycation End Product (AGE)-Receptor for AGE (RAGE) Signaling Inhibitors as Novel Therapeutic Strategies for Patients with AGE-Related Diseases | 作者: | CHIEH-YU SHEN CHENG-HSUN LU CHENG-HAN WU KO-JEN LI YU-MIN KUO SONG-CHOU HSIEH CHIA-LI YU |
關鍵字: | AGE-related diseases; AGE–RAGE axis signaling; Maillard reaction; Maillard reaction inhibitor; Nε(carboxyethyl)-lysine; Nε-(carboxymethyl)-lysine; advanced glycation end products; glyoxalase; metabolic memory; receptor for AGEs | 公開日期: | 27-十一月-2020 | 出版社: | MDPI | 卷: | 25 | 期: | 23 | 起(迄)頁: | 5591 | 來源出版物: | Molecules (Basel, Switzerland) | 摘要: | Advanced glycation end products (AGEs) are generated by nonenzymatic modifications of macromolecules (proteins, lipids, and nucleic acids) by saccharides (glucose, fructose, and pentose) via Maillard reaction. The formed AGE molecules can be catabolized and cleared by glyoxalase I and II in renal proximal tubular cells. AGE-related diseases include physiological aging, neurodegenerative/neuroinflammatory diseases, diabetes mellitus (DM) and its complications, autoimmune/rheumatic inflammatory diseases, bone-degenerative diseases, and chronic renal diseases. AGEs, by binding to receptors for AGE (RAGEs), alter innate and adaptive immune responses to induce inflammation and immunosuppression via the generation of proinflammatory cytokines, reactive oxygen species (ROS), and reactive nitrogen intermediates (RNI). These pathological molecules cause vascular endothelial/smooth muscular/connective tissue-cell and renal mesangial/endothelial/podocytic-cell damage in AGE-related diseases. In the present review, we first focus on the cellular and molecular bases of AGE-RAGE axis signaling pathways in AGE-related diseases. Then, we discuss in detail the modes of action of newly discovered novel biomolecules and phytochemical compounds, such as Maillard reaction and AGE-RAGE signaling inhibitors. These molecules are expected to become the new therapeutic strategies for patients with AGE-related diseases in addition to the traditional hypoglycemic and anti-hypertensive agents. We particularly emphasize the importance of "metabolic memory", the "French paradox", and the pharmacokinetics and therapeutic dosing of the effective natural compounds associated with pharmacogenetics in the treatment of AGE-related diseases. Lastly, we propose prospective investigations for solving the enigmas in AGE-mediated pathological effects. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/632649 | ISSN: | 1420-3049 | DOI: | 10.3390/molecules25235591 |
顯示於: | 醫學系 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。