ESR1: A Critical Factor in the Alzheimer’s Disease Process

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Aging (Aging-US)

Aging-US published this trending research paper in Volume 14, Issue 21, entitled, "ESR1 dysfunction triggers neuroinflammation as a critical upstream causative factor of the Alzheimer’s disease process" by researchers from NatPro Center, School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Ireland; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China; Department of Regenerative Medicine, School of Pharmaceutical Sciences, Jilin University, Changchun, China; School of Medicine, Trinity College Dublin, Ireland. DOI - https://doi.org/10.18632/aging.204359 Corresponding authors - Junying Liu - juliu@tcd.ie Abstract Alzheimer's disease (AD) accounts for approximately 60% of dementia cases worldwide. Advanced age is the most significant risk factor for AD and approximately two-thirds of cases relate to women. While the previous meta-analysis suggests that estrogen receptor (ESR) genetic polymorphisms are closely associated with dementia, the implications of this observation on a molecular level are not entirely understood. Our study explores this intricate molecular puzzle through the use of a variety of bioinformatics tools. Initially, we attempted to elucidate mechanisms underlying breast cancer development by identifying the high-throughput dataset of ESR1-knockdown breast cancer tissue samples. Surprisingly, KEGG pathway enrichment showed that the most frequently occurring proteins were related to axonal guidance and inflammation-related gene markers. These observations were supported by an external high throughput dataset of AD inflammatory samples in vivo. Our results suggest that ESR1 is modulated by apolipoprotein E (APOE) through CEBPB/ATF4, mir-155-5p, or mir-1-3p. Moreover, sea hare-hydrolysates (SHH), as one of the axonal guidance molecules, could regulate the STAT3/PRDM1/CEBPB pathway and consequently induce cell death through pyroptosis signaling pathways, trigger the secretion of IL1β, leading to neuroinflammation and worsening AD pathogenesis. Molecular docking verification demonstrated that the predicted natural products scoulerine and genistein displayed strong binding affinities for BACE1 and ESR1, respectively. This strategy can be used to design novel, personalized therapeutic approaches to treatment and a first-in-class clinical lead for the personalised treatment of AD. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204359 Keywords - ESR1, Alzheimer’s disease, CEBPB/ATF4, APOE, pyroptosis About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/agingus​ LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM