{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T12:04:18Z","timestamp":1791547458791,"version":"4.3.4"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"37","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,9,11]]},"abstract":"<jats:p>Treatment with either estradiol or an estrogen receptor (ER)\u03b1 ligand has been shown to be both antiinflammatory and neuroprotective in a variety of neurological disease models, but whether neuroprotective effects could be observed in the absence of an antiinflammatory effect has remained unknown. Here, we have contrasted effects of treatment with an ER\u03b1 vs. an ER\u03b2 ligand in experimental autoimmune encephalomyelitis, the multiple sclerosis model with a known pathogenic role for both inflammation and neurodegeneration. Clinically, ER\u03b1 ligand treatment abrogated disease at the onset and throughout the disease course. In contrast, ER\u03b2 ligand treatment had no effect at disease onset but promoted recovery during the chronic phase of the disease. ER\u03b1 ligand treatment was antiinflammatory in the systemic immune system, whereas ER\u03b2 ligand treatment was not. Also, ER\u03b1 ligand treatment reduced CNS inflammation, whereas ER\u03b2 ligand treatment did not. Interestingly, treatment with either the ER\u03b1 or the ER\u03b2 ligand was neuroprotective, as evidenced by reduced demyelination and preservation of axon numbers in white matter, as well as decreased neuronal abnormalities in gray matter. Thus, by using the ER\u03b2 selective ligand, we have dissociated the antiinflammatory effect from the neuroprotective effect of estrogen treatment and have shown that neuroprotective effects of estrogen treatment do not necessarily depend on antiinflammatory properties. Together, these findings suggest that ER\u03b2 ligand treatment should be explored as a potential neuroprotective strategy in multiple sclerosis and other neurodegenerative diseases, particularly because estrogen-related toxicities such as breast and uterine cancer are mediated through ER\u03b1.<\/jats:p>","DOI":"10.1073\/pnas.0703783104","type":"journal-article","created":{"date-parts":[[2007,9,4]],"date-time":"2007-09-04T20:41:08Z","timestamp":1188938468000},"page":"14813-14818","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":208,"title":["Differential neuroprotective and antiinflammatory effects of estrogen receptor (ER)\u03b1 and ER\u03b2 ligand treatment"],"prefix":"10.1073","volume":"104","author":[{"given":"Seema","family":"Tiwari-Woodruff","sequence":"first","affiliation":[{"name":"Multiple Sclerosis Program, Department of Neurology, David Geffen School of Medicine, University of California, Neuroscience Research Building 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