Long axons and their associated glia form the largest component of the neuronal network in the nervous system. Axon degeneration (AxD) and pathological glial alterations are an etiological hallmark of many neurodegenerative conditions. Protecting axons and their glia is therefore an important therapeutic target. Using a multi-disciplinary approach, our laboratory investigates the intriguing concept that the interplay between axonal and glial energy metabolism plays a central role in the regulation of axon integrity. Our overarching and long-term research goal is to elucidate the relationship of axonal bioenergetics and glial metabolism (axoglial metabolic coupling). We aim to identify specific metabolic functions of axon-flanking glia that are important for the support of axons under physiological and injury conditions. The knowledge gained from these studies has the potential for the design of novel treatment strategies for many neurodegenerative diseases that are associated with early AxD, and in which AxD results in the most prominent and irreversible symptoms.