Redox imbalance and metabolic defects in the context of Alzheimer disease

Redox reactions play a critical role for intracellular processes, including path- ways involved in metabolism and signaling. Reactive oxygen species (ROS) act either as second messengers or generators of protein modifications, funda- mental mechanisms for signal transduction. Disturbance of redox homeostasis is associated with many disorders. Among these, Alzheimer’s disease is a neu- rodegenerative pathology that presents hallmarks of oxidative damage such as increased ROS production, decreased activity of antioxidant enzymes, oxi- dative modifications of macromolecules, and changes in mitochondrial homeo- stasis. Interestingly, alteration of redox homeostasis is closely associated with defects of energy metabolism, involving both carbohydrates and lipids, the major energy fuels for the cell. As the brain relies exclusively on glucose metabolism, defects of glucose utilization represent a harmful event for the brain. During aging, a progressive perturbation of energy metabolism occurs resulting in brain hypometabolism. This condition contributes to increase neu- ronal cell vulnerability ultimately resulting in cognitive impairment. The cur- rent review discusses the crosstalk between alteration of redox homeostasis and brain energy defects that seems to act in concert in promoting Alzhei- mer’s neurodegeneration.