Purpose of review: Here, we discuss the recent developments in axonal mitochondrial response to demyelination and remyelination in multiple sclerosis (MS), and following experimental demyelination as well as myelination.
Recent findings: There is a gathering body of evidence implicating an energy-deficient state in the pathogenesis of MS, and mitochondrial defects have been the subject of a number of previous reviews. In myelinated axons within the central nervous system, over 90% of mitochondria are located within juxtaparanodal and internodal axoplasm. The electrogenic machinery, mitochondria and myelin form a triad that is disrupted in MS. The axonal mitochondrial content increases following demyelination and persists despite the residual inflammatory reaction subsiding to levels seen in control cases. The changes in axonal mitochondrial content following demyelination in MS and experimental demyelination in vivo and in vitro do not return to the levels in nondemyelinated and myelinated axons following remyelination.
Summary: Understanding the mechanisms of axonal mitochondrial response to a disturbance in myelin and determining if certain aspects of the axonal mitochondrial response to demyelinated and remyelinated axons are beneficial may identify potential therapeutic targets for the progressive forms of MS.