Neurotoxicity induced by glycotoxins

This chapter deals with the cytotoxic effects of advanced glycation end products (AGEs), referred to as glycotoxins, on neurons, which are particularly challenged by oxidative and carbonylic stresses due to their high metabolic rate, high reliance on mitochondrial oxidative phosphorylation, and low antioxidant defenses. Starting from the description of exogenous and endogenous AGEs formation, with a focus on methylglyoxal, the main precursor of AGEs, the chapter discusses the molecular mechanisms that can lead overall AGEs level to exceed a threshold value above which the cell is no longer capable of coping with AGEs burden. The detrimental effects of AGEs in brain aging and neurodegeneration, and the association among oxidative stress, glycotoxins, mitochondria, aging, and neurodegenerative diseases, as Alzheimer’s disease, are described. The chapter also stresses the importance of both therapeutic strategies targeting AGEs formation and low AGEs-containing diets to contrast neurodegeneration in both aging and neurodegenerative diseases.