Metabolic aspects of neuronal degeneration: From a NAD ⁺ point of view

Cellular metabolism maintains the life of cells, allowing energy production required for building cellular constituents and maintaining homeostasis under constantly changing external environments. Neuronal cells maintain their structure and function for the entire life of organisms and the loss of neurons, with limited neurogenesis in adults, directly causes loss of complexity in the neuronal networks. The nervous system organizes the neurons by placing cell bodies containing nuclei of similar types of neurons in discrete regions. Accordingly, axons must travel great distances to connect different types of neurons and peripheral organs. The enormous surface area of neurons makes them high-energy demanding to keep their membrane potential. Distal axon survival is dependent on axonal transport that is another energy demanding process. All of these factors make metabolic stress a potential risk factor for neuronal death and neuronal degeneration often associated with metabolic diseases. This review discusses recent findings on metabolic dysregulations under neuronal degeneration and pathways protecting neurons in these conditions.