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The Interaction Between NF-κB and Estrogen in Alzheimer’s Disease

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Abstract

Post-menopausal women are at a higher risk of developing Alzheimer’s disease (AD) than males. The higher rates of AD in women are associated with the sharp decline in the estrogen levels after menopause. Estrogen has been shown to downregulate inflammatory cytokines in the central nervous system (CNS), which has a neuroprotective role against neurodegenerative diseases including AD. Sustained neuroinflammation is associated with neurodegeneration and contributes to AD. Nuclear factor kappa-B (NF-κB) is a transcription factor involved with the modulation of inflammation and interacts with estrogen to influence the progression of AD. Application of 17β-estradiol (E2) has been shown to inhibit NF-κB, thereby reducing transcription of NF-κB target genes. Despite accumulating evidence showing that estrogens have beneficial effects in pre-clinical AD studies, there are mixed results with hormone replacement therapy in clinical trials. Furthering our understanding of how NF-κB interacts with estrogen and alters the progression of neurodegenerative disorders including AD, should be beneficial and result in the development of novel therapeutics.

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Data Availability

This is a review paper and no data was collected for this manuscript. However, the material supporting this paper is available in the article or is available from the corresponding author upon request.

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Acknowledgements

B.C.A. previously held the Manitoba Dementia Research Chair (funded by the Alzheimer’s Soc. of Manitoba and Research Manitoba) and the Honourable Douglas and Patricia Everett, Royal Canadian Properties Limited Endowment Chair.

Funding

We gratefully acknowledge the support from the St. Boniface Hospital Research Foundation (Grant Nos. 1406–3216 and 1410–3216), the Canadian Institute of Health Research (CIHR; Grant No. PJT-162144) to B.C.A., the Alzheimer’s Society of Manitoba, the Honourable Douglas and Patricia Everett, Royal Canadian Properties Limited Endowment Fund (Grant No. 1403–3131) to B.C.A. B.C.A. previously held the Manitoba Dementia Research Chair (funded by the Alzheimer’s Soc. of Manitoba and Research Manitoba).

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Authors and Affiliations

  1. Division of Neurodegenerative Disorders, St. Boniface Hospital Research, Winnipeg, MB, Canada

    Pranav Mishra & Benedict C. Albensi

  2. Department of Pharmacology & Therapeutics, College of Medicine, University of Manitoba, Winnipeg, MB, Canada

    Pranav Mishra & Benedict C. Albensi

  3. Department of Biology, York University, Toronto, ON, Canada

    Don A. Davies

  4. Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, USA

    Benedict C. Albensi

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Pranav Mishra and Don Davies created the outline and wrote much of the paper. Benedict C. Albensi supervised the writing, edited the manuscript, provided additional text and references when necessary.

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Correspondence to Benedict C. Albensi.

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Mishra, P., Davies, D.A. & Albensi, B.C. The Interaction Between NF-κB and Estrogen in Alzheimer’s Disease. Mol Neurobiol 60, 1515–1526 (2023). https://doi.org/10.1007/s12035-022-03152-3

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