Estrogens as potential therapeutic agents in multiple sclerosis.
The disease activity of multiple sclerosis (MS) is known to be ameliorated during pregnancy, and pregnancy is also found to be protective in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Estrogen levels increase during pregnancy and basic researches have shown that estrogens have immunomodulatory effects on immune cells. The importance of estrogen in pathogenic autoimmune diseases has also been demonstrated in EAE by altering hormone levels. Mice treated with estrogen experienced significantly decreased EAE severity and delayed onset of disease as a result of neuroprotective and anti-inflammatory effects. Brain atrophy has been detected at the early stages of MS by using MRI; thus, as a neuroprotective agent, estrogen might be effective against brain atrophy. Estrogen's effects are primarily mediated by the nuclear estrogen receptor (ER), and recent studies have shown the presence of nuclear ERs on the cells involved in the immune response. There have been some reports on genetic polymorphisms of ERs in MS. In this review paper, we discuss increasing evidence that points to a link between estrogen and MS. We also analyze the therapeutic potential of estrogens in MS and review current genetic studies on ER.
Niino
Masaaki
M
Department of Neurology, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kitaku, Sapporo, Japan. niino@med.hokudai.ac.jp
Hirotani
Makoto
M
Fukazawa
Toshiyuki
T
Kikuchi
Seiji
S
Sasaki
Hidenao
H
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism; D004967:Estrogens / Q000276:immunology* / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D007166:Immunosuppressive Agents / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009103:Multiple Sclerosis; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000150:complications* / Q000276:immunology; D018696:Neuroprotective Agents / Q000276:immunology; D010052:Ovariectomy; D018417:Th1 Cells / Q000276:immunology
D004967:Estrogens; D007166:Immunosuppressive Agents; D018696:Neuroprotective Agents; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9