The potential therapeutic role of statins in central nervous system autoimmune disorders.
3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitors, 'statins' are widely used oral cholesterol-lowering drugs. Statins competitively inhibit HMG-CoA reductase, the enzyme that catalyzes conversion of HMG-CoA to L-mevalonate, a key intermediate in cholesterol synthesis. Certain metabolites of mevalonate are also involved in posttranslational modification of specific proteins involved in cell proliferation and differentiation. Thus, statins have important biologic effects that may be independent of their cholesterol-reducing properties. Recent studies indicate that statins have antiinflammatory and neuroprotective properties which may be beneficial in the treatment of multiple sclerosis as well as other central nervous system (CNS) neurodegenerative diseases. This article will outline current experimental evidence that may suggest potential clinical benefits for patients with CNS autoimmune disorders. Ultimately, clinical trials will have to determine the safety and efficacy of statins in this patient population.
Stüve
O
O
Department of Neurology, University of California, San Francisco, 521 Parnassus Avenue, San Francisco, California 94143-0114, USA.
Youssef
S
S
Dunn
S
S
Slavin
A J
AJ
Steinman
L
L
Zamvil
S S
SS
D000818:Animals; D020274:Autoimmune Diseases of the Nervous System / Q000188:drug therapy*; D002465:Cell Movement / Q000187:drug effects; D002493:Central Nervous System Diseases / Q000188:drug therapy*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D009103:Multiple Sclerosis / Q000188:drug therapy; D009687:Nuclear Proteins; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics
D000949:Histocompatibility Antigens Class II; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators