{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T22:09:40Z","timestamp":1783548580275,"version":"3.55.0"},"reference-count":0,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2014,12,23]],"date-time":"2014-12-23T00:00:00Z","timestamp":1419292800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2014,12,23]]},"abstract":"<jats:p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory loss and disordered cognition. Women have a higher AD incidence than men, indicating that the declining estrogen levels during menopause may influence AD pathogenesis. However, the mechanism underlying estrogen's neuroprotective effect is not fully clarified and is complicated by the presence of several distinct estrogen receptor (ER) types and the identification of a growing number of ER splice variants. Thus, a deeper analysis of ERs could elucidate the role of estrogen in age-related cognitive changes. Intracellular calcium signaling cascades play a pivotal role in ER\u03b1 neuroprotection against AD. The ER\u03b1-mediated inhibition of Death domain-associated protein (Daxx) translocation and the combination of membrane ER\u03b1 and caveolin in caveolae may protect against AD. Moreover, the voltage-dependent anion channel (VDAC)\/ER\u03b1 association may be important for maintaining channel inactivation and may be relevant in neuronal preservation against A\u03b2 injury. Additionally, ER\u03b1 may prevent glutamate excitotoxic injury by A\u03b2 through estrogen signaling mechanisms. ER\u03b1 and IGF-IR co-activation may mediate neuroprotection, and many other growth factors and intracellular signaling responses triggered by ER\u03b1 may also play important roles in this process. Furthermore, details regarding the genes and mRNA variants of ER\u03b1 that are expressed in different parts of the human organs have been clarified recently. Therefore, here we review the literature to clarify the neuroprotective role of ER\u03b1. This review focuses on the potential mechanisms mediated by ER\u03b1 in the intracellular signaling events in nervous system cells, thereby clarifying ER\u03b1-mediated protection against AD.<\/jats:p>","DOI":"10.3233\/jad-141875","type":"journal-article","created":{"date-parts":[[2018,6,4]],"date-time":"2018-06-04T13:48:14Z","timestamp":1528120094000},"page":"1137-1148","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":64,"title":["Update on the Neuroprotective Effect of Estrogen Receptor Alpha Against Alzheimer's Disease"],"prefix":"10.1177","volume":"43","author":[{"given":"Yu-Long","family":"Lan","sequence":"first","affiliation":[{"name":"Department of Physiology, Dalian Medical University, Dalian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Physiology, Dalian Medical University, Dalian, China"},{"name":"Liaoning Engineering Technology Centre of Target-based Nature Products for Prevention and Treatment of Ageing-related Neurodegeneration, Dalian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physiology, Dalian Medical University, Dalian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2014,12,23]]},"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-141875","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-141875","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:01:22Z","timestamp":1777370482000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JAD-141875"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,12,23]]},"references-count":0,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2014,12,23]]}},"alternative-id":["10.3233\/JAD-141875"],"URL":"https:\/\/doi.org\/10.3233\/jad-141875","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,12,23]]}}}