Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients

Degeneration of chronically demyelinated axons is a major cause of irreversible neurological disability in multiple sclerosis (MS) patients. Development of neuroprotective therapies will require elucidation of the molecular mechanisms by which neurons and axons degenerate.

We report ultrastructural changes that support Ca2+-mediated destruction of chronically demyelinated axons in MS patients. We compared expression levels of 33,000 characterized genes in postmortem motor cortex from six control and six MS brains matched for age, sex, and postmortem interval. As reduced energy production is a major contributor to Ca2+-mediated axonal degeneration, we focused on changes in oxidative phosphorylation and inhibitory neurotransmission.