Oxidative stress and neurodegeneration

2. JUANA M. PASQUINI, LAURA A. PASQUINI AND HECTOR R. QUINTÁ

BIOCHEMISTRY OF OXIDATIVE STRESS

Wiley

Año: 2016; p. 1 - 21

Multiple sclerosis, a highly disseminated chronic inflammatorydemyelinating disease, entails progressive neuroaxonal degeneration and is oneof the most common causes of progressive disability affecting young people. Themechanisms involved in oxidative stress-mediated neurodegeneration in MSpatients include free radical production from different sources: (a)mitochondria forced to produce high levels of energy for axonal transport uponmyelin sheath loss, (b) immune cells activated upon demyelination andneurodegeneration, and (c) myelin deficiencies in producing ATP synthesisoutside mitochondria. In addition, oxidative stress is amplified by ironreleased into the extracellular space from myelin breakdown and degeneratedmacrophages and microglia. The normal neuronal polarization and development ineach region of the central nervous system depend on the normal function ofactin cytoskeleton dynamics. This dynamics is primarily affected when there isa 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, preventingoxidative stress is crucial to maintain the normal function of the centralnervous system.