Pathobiochemistry of Aging and Neurodegeneration: Deregulation of NAD+ Metabolism in Brain Cells.

NAD+ plays a pivotal role in energy metabolism and adaptation to external stimuli and stressful conditions. A significant reduction in intracellular NAD+ levels is associated with aging and contributes to the development of chronic cardiovascular, neurodegenerative, and metabolic diseases. It is of particular importance to maintain optimal levels of NAD+ in cells with high energy consumption, particularly in the brain. Maintaining the tissue level of NAD+ with pharmacological tools has the potential to slow down the aging process, to prevent the development of age-related diseases. This review covers key aspects of NAD+ metabolism in terms of brain metabolic plasticity, including NAD+ biosynthesis and degradation in different types of brain cells, as well as its contribution to the development of neurodegeneration and aging, and highlights up-to-date approaches to modulate NAD+ levels in brain cells.