ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2022
Sex-Specific Regulation of β-Secretase: A Novel Estrogen Response Element (ERE)-Dependent Mechanism in Alzheimer's Disease.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Is Hormone Replacement Therapy a Risk Factor or a Therapeutic Option for Alzheimer's Disease?International journal of molecular sciences · 2023Pooled it
- Age-dependent biphasic alterations and protein-activity decoupling of plasma BACE1 in major depressive disorder.Frontiers in psychiatry · 2026Article
- Microglial interferon signaling and Aβ plaque pathology are enhanced in female 5xFAD Alzheimer's disease mice, independent of estrous cycle stage.Journal of neuroinflammation · 2025Article
- Differences in inflammatory markers, mitochondrial function, and synaptic proteins in male and female Alzheimer's disease post mortem brains.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Application of the Trend of miRNA Expression Levels in APP/PS1 Mice Plasma for the Early Diagnosis of Alzheimer's Disease.Molecular neurobiology · 2025Article
- Gelsolin Facilitates Estrogen Receptor Beta Nuclear Translocation and Transcriptional Repression of Genes Associated with Alzheimer Disease.Receptors (Basel, Switzerland) · 2025Article
- Serum β-secretase 1 (sBACE1) activity in subjective cognitive decline: an exploratory study.GeroScience · 2025Article
- Biological Sex Disparities in Alzheimer's Disease.Current topics in behavioral neurosciences · 2025Review
- Sex Differences in Blood Accumulation of Neurodegenerative-Related Proteins and Antioxidant Responses to Regular Physical Exercise.Journal of molecular neuroscience : MN · 2024Article
- A case for seeking sex-specific treatments in Alzheimer's disease.Frontiers in aging neuroscience · 2024Review
- Towards a Unitary Hypothesis of Alzheimer's Disease Pathogenesis.Journal of Alzheimer's disease : JAD · 2024Article
- A Novel Strategy for Alzheimer's Disease Based on the Regulatory Effect of Amyloid-β on Gut Flora.Journal of Alzheimer's disease : JAD · 2023Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Women have a higher prevalence and incidence of Alzheimer's disease (AD) than age-matched men, and loss of estrogen might be partially responsible for the higher risk of AD in aged women. While β-secretase (BACE1) plays an important role in AD pathogenesis, whether BACE1 involved the sex difference in AD pathology remains unclear. This study investigated the hypothesis that estrogen regulates BACE1 transcription via the estrogen response element (ERE) and designated pathways. Using estrogen receptor (ER) knock-out mice and mutagenesis of EREs in HEK293 cells, we demonstrated sex-specific inhibition of BACE1 transcription by estrogen via direct binding to ERE sites and ERα. We also used a repressor of estrogen receptor activity (REA) and showed that an REA-ERE complex downregulated BACE1. A chromatin immunoprecipitation assay analysis determined that all three EREs at the BACE1 promoter were required for estradiol-mediated downregulation of BACE1 transcription in mice. Last, we confirmed the impairment of the REA pathway in the cortex of female AD patients. Our study identified an estrogen-specific BACE1 transcriptional regulation pathway from cell and animal models to AD patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.