ArticleThe Journal of biological chemistry2010
Estrogen stimulates degradation of beta-amyloid peptide by up-regulating neprilysin.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 106 citations in OpenAlex.
- Elevated plasma sex hormone-binding globulin (SHBG) is associated with reduced temporal lobe volume and cognitive impairment in individuals with mild cognitive impairment.European geriatric medicine · 2026Article
- Estradiol ameliorates AD pathology and cognitive deficits by SORLA-mediated APP endosomal trafficking.Alzheimer's research & therapy · 2026Article
- Loss of ovarian hormones is detrimental in early disease stages of mouse models of Alzheimer's disease and multi-etiology dementia.Biology of sex differences · 2025Article
- Network pharmacology mechanism of Rosmarinus officinalis L.(Rosemary) to improve cell viability and reduces apoptosis in treating Alzheimer's disease.BMC complementary medicine and therapies · 2025Article
- Interactions between menopause and high-fat diet on cognition and pathology in a mouse model of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Gut microbiota has the potential to improve health of menopausal women by regulating estrogen.Frontiers in endocrinology · 2025Review
- Cerebral amyloid angiopathy: a narrative review.Frontiers in aging neuroscience · 2025Review
- Association of Circulating Neprilysin with BMI, Cardiovascular Health, and Kidney Function in High-Risk Pregnancies: A Pilot Study.Biomedicines · 2024Article
- The Role of Estrogen across Multiple Disease Mechanisms.Current issues in molecular biology · 2024Review
- Locally Synthetized 17-β-Estradiol Reverses Amyloid-β-42-Induced Hippocampal Long-Term Potentiation Deficits.International journal of molecular sciences · 2024Article
- Minding the Gap: Exploring Neuroinflammatory and Microglial Sex Differences in Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Risk Factors and Cellular Differences in Heart Failure: The Key Role of Sex Hormones.Biomedicines · 2023Review
- Expression and function of estrogen receptors and estrogen-related receptors in the brain and their association with Alzheimer's disease.Frontiers in endocrinology · 2023Review
- Association of biological sex with clinical outcomes and biomarkers of Alzheimer's disease in adults with Down syndrome.Brain communications · 2023Article
- Sex differences in hippocampal β-amyloid accumulation in the triple-transgenic mouse model of Alzheimer's disease and the potential role of local estrogens.Frontiers in neuroscience · 2023Article
- Association of vitamin D receptor gene haplotypes with late-onset Alzheimer's disease in a Southeastern European Caucasian population.Experimental and therapeutic medicine · 2022Article
- Sex Differences in Magnetoencephalography-Identified Functional Connectivity in the Human Connectome Project Connectomics of Brain Aging and Dementia Cohort.Brain connectivity · 2022Article
- Impact of increased APP gene dose in Down syndrome and the Dp16 mouse model.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Article
- Traditional Chinese Medicine as a Promising Strategy for the Treatment of Alzheimer's Disease Complicated With Osteoporosis.Frontiers in pharmacology · 2022Review
- Endogenous and Exogenous Estrogen Exposures: How Women's Reproductive Health Can Drive Brain Aging and Inform Alzheimer's Prevention.Frontiers in aging neuroscience · 2022Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Postmenopausal estrogen depletion is a characterized risk factor for Alzheimer disease (AD), a human disorder linked to high levels of beta-amyloid peptide (Abeta) in brain tissue. Previous studies suggest that estrogen negatively regulates the level of Abeta in the brain, but the molecular mechanism is unknown. Here, we provide evidence that estrogen promotes Abeta degradation mainly through a principal Abeta degrading enzyme, neprilysin, in neuroblastoma SH-SY5Y cells. We also demonstrate that up-regulation of neprilysin by estrogen is dependent on both estrogen receptor alpha and beta (ERalpha and ERbeta), and ligand-activated ER regulates expression of neprilysin through physical interactions between ER and estrogen response elements (EREs) identified in the neprilysin gene. These results were confirmed by in vitro gel shift and in vivo chromatin immunoprecipitation analyses, which demonstrate specific binding of ERalpha and ERbeta to two putative EREs in the neprilysin gene. The EREs also enhance ERalpha- and ERbeta-dependent reporter gene expression in a yeast model system. Therefore, the study described here provides a putative mechanism by which estrogen positively regulates expression of neprilysin to promote degradation of Abeta, reducing risk for AD. These results may lead to novel approaches to prevent or treat AD.
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