Radical changes in multiple sclerosis pathogenesis.
Reactive oxygen species (ROS) contain one or more unpaired electrons and are formed as intermediates in a variety of normal biochemical reactions. However, when generated in excess amounts or not appropriately controlled, ROS initiate extensive cellular damage and tissue injury. ROS have been implicated in the progression of cancer, cardiovascular disease and neurodegenerative and neuroinflammatory disorders, such as multiple sclerosis (MS). In the last decade there has been a major interest in the involvement of ROS in MS pathogenesis and evidence is emerging that free radicals play a key role in various processes underlying MS pathology. To counteract ROS-mediated damage, the central nervous system is equipped with an intrinsic defense mechanism consisting of endogenous antioxidant enzymes. Here, we provide a comprehensive overview on the (sub)cellular origin of ROS during neuroinflammation as well as the detrimental effects of ROS in processing underlying MS lesion development and persistence. In addition, we will discuss clinical and experimental studies highlighting the therapeutic potential of antioxidant protection in the pathogenesis of MS.
van Horssen
Jack
J
Departments of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands. j.vanhorssen@vumc.nl
Witte
Maarten E
ME
Schreibelt
Gerty
G
de Vries
Helga E
HE
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D017628:Microglia / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000975:Antioxidants; D005609:Free Radicals; D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species