Abstract
Methylglyoxal (MGO), a by-product of glycolysis, plays a significant role in cellular metabolism, particularly under stress conditions. However, MGO is a potent glycotoxin, and its accumulation has been linked to the development of several pathological conditions due to oxidative stress, including diabetes mellitus and neurodegenerative diseases. This paper focuses on the biochemical mechanisms by which MGO contributes to oxidative stress, particularly through the formation of advanced glycation end products (AGEs), its interactions with antioxidant systems, and its involvement in chronic diseases like diabetes, neurodegeneration, and cardiovascular disorders. MGO exerts its effects through multiple signaling pathways, including NF-κB, MAPK, and Nrf2, which induce oxidative stress. Additionally, MGO triggers apoptosis primarily via intrinsic and extrinsic pathways, while endoplasmic reticulum (ER) stress is mediated through PERK-eIF2α and IRE1-JNK signaling. Moreover, the activation of inflammatory pathways, particularly through RAGE and NF-κB, plays a crucial role in the pathogenesis of these conditions. This study points out the connection between oxidative and carbonyl stress due to increased MGO formation, and it should be an incentive to search for a marker that could have prognostic significance or could be a targeted therapeutic intervention in various diseases.