Neuroprotective effects of estrogens and androgens in CNS inflammation and neurodegeneration.
Multiple sclerosis (MS) is a disease characterized by inflammation and demyelination. Currently, the cause of MS is unknown. Experimental autoimmune encephalomyelitis (EAE) is the most common mouse model of MS. Treatments with the sex hormones, estrogens and androgens, are capable of offering disease protection during EAE and are currently being used in clinical trials of MS. Beyond endogenous estrogens and androgens, treatments with selective estrogen receptor modulators (SERMs) for estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) are also capable of providing disease protection. This protection includes, but is not limited to, prevention of clinical disease, reduction of CNS inflammation, protection against demyelination, and protection against axonal loss. In EAE, current efforts are focused on using conditional cell specific knockouts of sex hormone receptors to identify the in vivo targets of these estrogens and androgens as well as downstream molecules responsible for disease protection.
University of California, Los Angeles, Department of Neurology, UCLA Multiple Sclerosis Program, 635 Charles E Young Drive South, Neuroscience Research Building 1, Room 479, Los Angeles, CA 90095, United States. rory.spence@ucla.edu
Rory D
RD
Spence
Rhonda R
RR
Voskuhl
D000818:Animals; D002493:Central Nervous System Diseases / Q000188:drug therapy; D013196:Dihydrotestosterone / Q000627:therapeutic use; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D004958:Estradiol / Q000627:therapeutic use; D004964:Estriol / Q000627:therapeutic use; D047628:Estrogen Receptor alpha / Q000502:physiology; D047629:Estrogen Receptor beta / Q000502:physiology; D004967:Estrogens / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D051379:Mice; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011247:Pregnancy; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use; D013045:Species Specificity; D013739:Testosterone / Q000627:therapeutic use
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D018696:Neuroprotective Agents; D020845:Selective Estrogen Receptor Modulators; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol; D004964:Estriol