Estrogen Signaling in Alzheimer’s Disease: Molecular Insights and Therapeutic Targets for Alzheimer’s Dementia
Estrogens play a crucial physiological function in the brain; however, debates exist concerning the role of estrogens in Alzheimer’s disease (AD). Women during pre-, peri-, or menopause periods are more susceptible for developing AD, suggesting the connection of sex factors and a decreased estrogen...
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| Veröffentlicht in: | Molecular neurobiology 2020-06, Vol.57 (6), p.2654-2670 |
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| creator | Uddin, Md. Sahab Rahman, Md. Motiar Jakaria, Md Rahman, Md. Sohanur Hossain, Md. Sarwar Islam, Ariful Ahmed, Muniruddin Mathew, Bijo Omar, Ulfat Mohammed Barreto, George E. Ashraf, Ghulam Md |
| description | Estrogens play a crucial physiological function in the brain; however, debates exist concerning the role of estrogens in Alzheimer’s disease (AD). Women during pre-, peri-, or menopause periods are more susceptible for developing AD, suggesting the connection of sex factors and a decreased estrogen signaling in AD pathogenesis. Yet, the underlying mechanism of estrogen-mediated neuroprotection is unclarified and is complicated by the existence of estrogen-related factors. Consequently, a deeper analysis of estrogen receptor (ER) expression and estrogen-metabolizing enzymes could interpret the importance of estrogen in age-linked cognitive alterations. Previous studies propose that hormone replacement therapy may attenuate AD onset in postmenopausal women, demonstrating that estrogen signaling is important for the development and progression of AD. For example, ERα exerts neuroprotection against AD by maintaining intracellular signaling cascades and study reported reduced expression of ERα in hippocampal neurons of AD patients. Similarly, reduced expression of ERβ in female AD patients has been associated with abnormal function in mitochondria and improved markers of oxidative stress. In this review, we discuss the critical interaction between estrogen signaling and AD. Moreover, we highlight the potential of targeting estrogen-related signaling for therapeutic intervention in AD. |
| doi_str_mv | 10.1007/s12035-020-01911-8 |
| format | Article |
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Sahab ; Rahman, Md. Motiar ; Jakaria, Md ; Rahman, Md. Sohanur ; Hossain, Md. Sarwar ; Islam, Ariful ; Ahmed, Muniruddin ; Mathew, Bijo ; Omar, Ulfat Mohammed ; Barreto, George E. ; Ashraf, Ghulam Md</creator><creatorcontrib>Uddin, Md. Sahab ; Rahman, Md. Motiar ; Jakaria, Md ; Rahman, Md. Sohanur ; Hossain, Md. Sarwar ; Islam, Ariful ; Ahmed, Muniruddin ; Mathew, Bijo ; Omar, Ulfat Mohammed ; Barreto, George E. ; Ashraf, Ghulam Md</creatorcontrib><description>Estrogens play a crucial physiological function in the brain; however, debates exist concerning the role of estrogens in Alzheimer’s disease (AD). Women during pre-, peri-, or menopause periods are more susceptible for developing AD, suggesting the connection of sex factors and a decreased estrogen signaling in AD pathogenesis. Yet, the underlying mechanism of estrogen-mediated neuroprotection is unclarified and is complicated by the existence of estrogen-related factors. Consequently, a deeper analysis of estrogen receptor (ER) expression and estrogen-metabolizing enzymes could interpret the importance of estrogen in age-linked cognitive alterations. Previous studies propose that hormone replacement therapy may attenuate AD onset in postmenopausal women, demonstrating that estrogen signaling is important for the development and progression of AD. For example, ERα exerts neuroprotection against AD by maintaining intracellular signaling cascades and study reported reduced expression of ERα in hippocampal neurons of AD patients. Similarly, reduced expression of ERβ in female AD patients has been associated with abnormal function in mitochondria and improved markers of oxidative stress. In this review, we discuss the critical interaction between estrogen signaling and AD. Moreover, we highlight the potential of targeting estrogen-related signaling for therapeutic intervention in AD.</description><identifier>ISSN: 0893-7648</identifier><identifier>EISSN: 1559-1182</identifier><identifier>DOI: 10.1007/s12035-020-01911-8</identifier><identifier>PMID: 32297302</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Age ; Alzheimer Disease - metabolism ; Alzheimer's disease ; Biomedical and Life Sciences ; Biomedicine ; Brain - metabolism ; Cell Biology ; Cognitive ability ; Dementia ; Dementia disorders ; Estrogen receptors ; Estrogens ; Estrogens - metabolism ; Health risk assessment ; Hippocampus ; Hormone replacement therapy ; Humans ; Intracellular signalling ; Menopause ; Mitochondria ; Neurobiology ; Neurodegenerative diseases ; Neurology ; Neurons - metabolism ; Neuroprotection ; Neurosciences ; Oxidative stress ; Post-menopause ; Receptors, Estrogen - metabolism ; Signal Transduction - physiology ; Therapeutic applications</subject><ispartof>Molecular neurobiology, 2020-06, Vol.57 (6), p.2654-2670</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2020</rights><rights>Springer Science+Business Media, LLC, part of Springer Nature 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-f3ed03b33550342954ed8927ac92a6b622d33e2335dc75fe3caa5cd8beb40f363</citedby><cites>FETCH-LOGICAL-c375t-f3ed03b33550342954ed8927ac92a6b622d33e2335dc75fe3caa5cd8beb40f363</cites><orcidid>0000-0002-0805-7840</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12035-020-01911-8$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12035-020-01911-8$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32297302$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Uddin, Md. 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Women during pre-, peri-, or menopause periods are more susceptible for developing AD, suggesting the connection of sex factors and a decreased estrogen signaling in AD pathogenesis. Yet, the underlying mechanism of estrogen-mediated neuroprotection is unclarified and is complicated by the existence of estrogen-related factors. Consequently, a deeper analysis of estrogen receptor (ER) expression and estrogen-metabolizing enzymes could interpret the importance of estrogen in age-linked cognitive alterations. Previous studies propose that hormone replacement therapy may attenuate AD onset in postmenopausal women, demonstrating that estrogen signaling is important for the development and progression of AD. For example, ERα exerts neuroprotection against AD by maintaining intracellular signaling cascades and study reported reduced expression of ERα in hippocampal neurons of AD patients. Similarly, reduced expression of ERβ in female AD patients has been associated with abnormal function in mitochondria and improved markers of oxidative stress. In this review, we discuss the critical interaction between estrogen signaling and AD. 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Sahab</au><au>Rahman, Md. Motiar</au><au>Jakaria, Md</au><au>Rahman, Md. Sohanur</au><au>Hossain, Md. Sarwar</au><au>Islam, Ariful</au><au>Ahmed, Muniruddin</au><au>Mathew, Bijo</au><au>Omar, Ulfat Mohammed</au><au>Barreto, George E.</au><au>Ashraf, Ghulam Md</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Estrogen Signaling in Alzheimer’s Disease: Molecular Insights and Therapeutic Targets for Alzheimer’s Dementia</atitle><jtitle>Molecular neurobiology</jtitle><stitle>Mol Neurobiol</stitle><addtitle>Mol Neurobiol</addtitle><date>2020-06-01</date><risdate>2020</risdate><volume>57</volume><issue>6</issue><spage>2654</spage><epage>2670</epage><pages>2654-2670</pages><issn>0893-7648</issn><eissn>1559-1182</eissn><abstract>Estrogens play a crucial physiological function in the brain; however, debates exist concerning the role of estrogens in Alzheimer’s disease (AD). 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| subjects | Age Alzheimer Disease - metabolism Alzheimer's disease Biomedical and Life Sciences Biomedicine Brain - metabolism Cell Biology Cognitive ability Dementia Dementia disorders Estrogen receptors Estrogens Estrogens - metabolism Health risk assessment Hippocampus Hormone replacement therapy Humans Intracellular signalling Menopause Mitochondria Neurobiology Neurodegenerative diseases Neurology Neurons - metabolism Neuroprotection Neurosciences Oxidative stress Post-menopause Receptors, Estrogen - metabolism Signal Transduction - physiology Therapeutic applications |
| title | Estrogen Signaling in Alzheimer’s Disease: Molecular Insights and Therapeutic Targets for Alzheimer’s Dementia |
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