title: Targeting estrogen receptors for the treatment of Alzheimer's disease.
abstract: The significantly higher incidence of Alzheimer's disease (AD) in women than in men has been attributed to loss of estrogen and a variety of related mechanisms at the molecular, cellular, and hormonal levels, which subsequently elucidate neuroprotective roles of estrogen against AD-related pathology. Recent studies have proposed that beneficial effects of estrogen on AD are directly linked to its ability to reduce amyloid-β peptides and tau aggregates, two hallmark lesions of AD. Despite high expectations, large clinical trials with postmenopausal women indicated that the beneficial effects of estrogen therapies were insignificant and, in fact, elicited adverse effects. Here, we review the current status of AD prevention and treatment using estrogens focusing on recent understandings of their biochemical links to AD pathophysiology. This review also discusses development of selective ligands that specifically target either estrogen receptor α (ERα) or ERβ isoforms, which are potentially promising strategies for safe and efficient treatment of AD.
authors.affiliation: Department of Applied Chemistry, College of Applied Sciences, Kyung Hee University, Yongin, 446-701, Republic of Korea.
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: Yanxialei
authors.initials: Y
authors.lastname: Jiang
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Han
authors.forename: Seung Kyun
authors.initials: SK
authors.lastname: Shin
authors.forename: Won Hoon
authors.initials: WH
authors.lastname: Choi
authors.forename: Min Jae
authors.initials: MJ
authors.lastname: Lee
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism*; D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D020033:Protein Isoforms / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000378:metabolism*; D016896:Treatment Outcome; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D047628:Estrogen Receptor alpha; D008024:Ligands; D020033:Protein Isoforms; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D000097983:ERRalpha Estrogen-Related Receptor; C490918:ESRRB protein, human