Multiple sclerosis (MS) is an autoimmune disorder that results in incurable disabilities. Now, groundbreaking research conducted by Leipzig University and the Max Planck Institute has posed a new working model of how the immune system’s activity leads to axon damage. Their findings flip the script on MS and provide a fresh perspective on its manifestation.
Schaffner et al., Nature Neuroscience 2023
Oligodendrocytes create myelin sheaths, which are responsible for shielding and enhancing the efficiency of the long axons of neurons. According to our current understanding of MS, when the immune system attacks oligodendrocytes, myelin is removed and the axons are exposed to detrimental inflammation.
However, an intriguing discrepancy remained. If the loss of myelin-coated axons is solely responsible for MS progression, why do we see MS symptoms before myelination loss occurs? This puzzling question prompted scientists to dig deeper and rethink the existing model.
Using a combination of mouse models and human tissue samples, the research team simulated an autoimmune attack to investigate the effects. Astonishingly, electron microscopy images unveiled those neurons still “protected” by myelin suffered the most extensively damaged. Though lacking the benefits of myelin coats, naked neurons fared better in the acute inflammatory environment.
Perhaps the presence of damaged myelin inflicts axonal damage, contrary to previous assumptions. Like a vending machine that has fallen on top of you, the previous source of sustenance now threatens your survival.
Professor Klaus-Armin Nave of the Max Planck Institute for Multidisciplinary Sciences in Göttingen, Germany, explains the order of operations: “When oligodendrocytes are exposed to an acute inflammatory environment, they may lose their ability to support the axons, and myelin becomes a threat to the survival of the axons” (via EurekAltert!)
Schaffner et al., Nature Neuroscience 2023
By identifying a crucial component of MS, researchers have revealed a promising avenue for future therapeutic interventions. “Instead of preserving the damaged myelin,” says Dr. Robert Fledrich from the Institute of Anatomy at Leipzig University, “it might actually be therapeutically better to promote rapid degradation of damaged myelin.” With the wrecked vending machine removed, encouraging "regeneration of functional myelin" may alleviate MS symptoms.
Sources: Nature Neuroscience, EurekAltert!
