An emerging role of dysfunctional axon-oligodendrocyte coupling in neurodegenerative diseases

Myelin is made by highly specialized glial cells and enables fast axonal impulse propagation. Recent studies show that oligodendrocytes in the central nervous system are, in addition to myelination, required for the integrity and survival of axons, independent of the presence or absence of myelin itself. The underlying mechanism of this support is given by glycolytic oligodendrocytes which provide axons with energy-rich metabolites. These findings represent a paradigm shift for the physiological function of axon-associated glia, and open the intriguing possibility that oligodendrocytes are important contributors to neurodegenerative diseases in which myelinated axons are lost, such as in Alzheimer disease, amyotrophic lateral sclerosis, and multiple system atrophy. Understanding the role of axon-oligodendrocyte coupling in neurodegenerative diseases may pave the way for the development of metabolism-based therapeutic approaches.