Oxidative Stress and Neurodegeneration

Multiple sclerosis, a highly disseminated chronic inflammatory demyelinating disease, entails progressive neuroaxonal degeneration and is one of the most common causes of progressive disability affecting young people. The mechanisms involved in oxidative stress-mediated neurodegeneration in MS patients include free radical production from different sources: (a) mitochondria forced to produce high levels of energy for axonal transport upon myelin sheath loss, (b) immune cells activated upon demyelination and neurodegeneration, and (c) myelin deficiencies in producing ATP synthesis outside mitochondria. In addition, oxidative stress is amplified by iron released into the extracellular space from myelin breakdown and degenerated macrophages and microglia. The normal neuronal polarization and development in each region of the central nervous system depend on the normal function of actin cytoskeleton dynamics. This dynamics is primarily affected when there is a deregulation in the intraneuronal production of reactive oxygen species. These reactive oxygen species promote oxidation of filamentous actin (cytoskeleton depolymerization) and, therefore, axonal collapse. In summary, preventing oxidative stress is crucial to maintain the normal function of the central nervous system.