MS and Mitochondrial Dysfunction

Multiple sclerosis (MS) is an autoimmune disorder that leads to demyelination (damage to the myelin sheaths surrounding nerve fibers) and clinical debilitation. This is the conventional medical wisdom. New research is shedding light on other data that may change how we understand MS. In addition to the neurodegenerative processes of MS, mitochondrial dysfunction is a key contributing mechanism. This may happen due to increased permeability of the transition pore opening and calcium dysregulation, which are central to mitochondrial dysfunction and neurodegeneration in MS.

Let’s take a deeper dive into this new way of understanding MS.

Mitochondrial dysfunction and neurodegeneration in MS

Scientists are investigating mitochondrial dysfunction to explain the diffuse neurodegeneration found in MS patients. Mitochondria are involved in ATP synthesis and calcium regulation. They are also a major source of reactive oxygen species (ROS). This, mitochondrial dysfunction could lead to insufficient energy production and intracellular dysregulation. This type of dysfunction is particularly damaging to neurons given their dependence on ATP to generate electrical signals, facilitate transportation along axons, and maintain ionic gradients.

Evidence of mitochondrial dysfunction in MS is growing. For instance, NAA, the commonly used MRS marker of neuronal integrity, is produced by neuronal mitochondria. Therefore, changes in NAA levels can also reflect mitochondrial dysfunction within neurons.

Alterations in NAA levels are linked with relapses. These changes fall significantly in acute inflammatory lesions, and they partially reverse as inflammation lessens. The initial decline in NAA points to reversible mitochondrial dysfunction in neurons within these acute lesions. Similar decreases of NAA in NAWM and focal white matter lesions may also point to mitochondrial dysfunction within the neurons. Scientists have also found evidence of mitochondrial dysfunction linked to neurodegeneration. And they have found evidence of oxidative damage of mitochondrial DNA along with the impaired activity of mitochondrial enzymes. Several studies have shown structural damage in the earliest phases giving researchers convincing evidence that mitochondrial function may play a significant role in MS neurodegenerative mechanisms.