title: Multiple sclerosis is not a disease of the immune system.
abstract: Multiple sclerosis is a complex neurodegenerative disease, thought to arise through autoimmunity against antigens of the central nervous system. The autoimmunity hypothesis fails to explain why genetic and environmental risk factors linked to the disease in one population tend to be unimportant in other populations. Despite great advances in documenting the cell and molecular mechanisms underlying MS pathophysiology, the autoimmunity framework has also been unable to develop a comprehensive explanation of the etiology of the disease. I propose a new framework for understanding MS as a dysfunction of the metabolism of lipids. Specifically, the homeostasis of lipid metabolism collapses during acute-phase inflammatory response triggered by a pathogen, trauma, or stress, starting a feedback loop of increased oxidative stress, inflammatory response, and proliferation of cytoxic foam cells that cross the blood brain barrier and both catabolize myelin and prevent remyelination. Understanding MS as a chronic metabolic disorder illuminates four aspects of disease onset and progression: 1) its pathophysiology; 2) genetic susceptibility; 3) environmental and pathogen triggers; and 4) the skewed sex ratio of patients. It also suggests new avenues for treatment.
authors.affiliation: Department of Sciences, John Jay College of Criminal Justice, City University of New York New York, New York 10019, USA. acorthals@jjay.cuny.edu
authors.forename: Angelique P
authors.initials: AP
authors.lastname: Corthals
mesh_terms: D005227:Fatty Acids / Q000378:metabolism; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism; D050356:Lipid Metabolism; D009103:Multiple Sclerosis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D020675:Peroxisomes / Q000378:metabolism; D012307:Risk Factors; D017678:Sex Distribution
chemical_list: D005227:Fatty Acids; D047492:Peroxisome Proliferator-Activated Receptors