Targeting mitochondria to protect axons in progressive MS

Inflammatory demyelinating processes target the neuron, particularly axons and synapses, in multiple sclerosis (MS). There is a gathering body of evidence indicating molecular changes which converge on mitochondria within neurons in progressive forms of MS. The most reproducible changes are the increase in mitochondrial content within demyelinated axons and mitochondrial respiratory chain complex deficiency in neurons, which compromises the capacity to generate ATP. The resulting lack of ATP and the likely energy failure state and its coupling with an increase in demand for energy by the demyelinated axon, are particularly relevant to the long tracts such as corticospinal tracts with long projection axons. Recent work in our laboratory and that of our collaborators indicate the limited reflection of the mitochondrial changes within neurons in the experimental disease models. Enhancing the energy producing capacity of neurons to meet the increased energy demand of demyelinated axons is likely to be a novel neuroprotective strategy in progressive MS.