Synaptic ATPases and energy metabolism in the nervous system: Roles and changes during aging

In this paper, we review the in vivo experimental studies investigating the neuronal mechanisms of brain bioenergetics, in an attempt to understand the biochemical changes of Functional Proteomics and Metabolomics specifically related to the enzyme systems linked to energy transduction during physiological and pathological aging. The availability of adenosine triphosphate, as the main energy source for cerebral tissue, is regulated by the activity of key enzymes of specific metabolic pathways, located in subcellular structures of neurons, e.g., mainly different types of mitochondria and selected synaptic plasma membranes. The analysis of the catalytic properties of energy-yielding enzyme systems of mitochondria (Krebs Cycle and Electron Transfer Chain) with respect to energy-utilizing enzyme systems of synaptic ATPases were examined during aging, also in the perspective of a neuropharmacological approach for the evaluation of potential therapies against diseases affecting the central nervous system. Moreover, we point out the significance of conducting these types of studies according to a subcellular approach and considering the so-called metabolic mosaic that characterizes brain tissue. The clarification of molecular mechanisms affecting the neuronal bioenergetic systems of synaptic mitochondrial enzymes and ATPases will greatly improve the understanding of human brain energy metabolism, particularly during aging, i.e., the main and not modifiable risk factor for many neurological and psychiatric pathologies.