ArticleAging cell2015
Opposite effects of two estrogen receptors on tau phosphorylation through disparate effects on the miR-218/PTPA pathway.
Article in Aging cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
32 citing papers in PubMed, 54 citations in OpenAlex.
- Estradiol ameliorates AD pathology and cognitive deficits by SORLA-mediated APP endosomal trafficking.Alzheimer's research & therapy · 2026Article
- Advances and Therapeutic Potential of Anthraquinone Compounds in Neurodegenerative Diseases: A Comprehensive Review.Drug design, development and therapy · 2026Review
- Beyond Estrogen: Unraveling the Complexities of Hormonal Signaling Pathways in Alzheimer's Disease and Their Implications for Precision Therapy.Molecular neurobiology · 2025Review
- Equol as a Multitarget Agent Against Neurodegeneration: Mechanistic Insights into Its Molecular Modulation.Neuromolecular medicine · 2025Review
- Not your mother's hormone therapy: Highly selective estrogen receptor beta agonists as next-generation therapies for menopausal symptom relief.Hormones and behavior · 2025Review
- The Abnormal ERα-miRNA Cross-Talk in AD-Affected Human Hippocampus: A Bioinformatics Perspective.Molecular neurobiology · 2025Article
- Suppression of miR-218 promotes SOCS3 expression to alleviate cognitive impairment and white matter injury after chronic cerebral hypoperfusion.Metabolic brain disease · 2025Article
- Historical loss weakens competitive behavior by remodeling ventral hippocampal dynamics.Cell discovery · 2025Article
- The Immunomodulatory Role of Estrogen in Malaria: A Review of Sex Differences and Therapeutic Implications.Immunity, inflammation and disease · 2025Review
- Cpeb1 remodels cell type-specific translational program to promote fear extinction.Science advances · 2025Article
- The Role of Estrogen in Brain MicroRNAs Regulation.Advanced pharmaceutical bulletin · 2024Review
- Untangling the role of tau in sex hormone responsive cancers: lessons learnt from Alzheimer's disease.Clinical science (London, England : 1979) · 2024Review
- Estrogen Receptors: A New Frontier in Alzheimer's Disease Therapy.International journal of molecular sciences · 2024Review
- The novel estrogen receptor beta agonist EGX358 andFrontiers in aging neuroscience · 2024Article
- Triptolide improves Alzheimer's disease by regulating the NF‑κB signaling pathway through the lncRNA NEAT1/microRNA 361‑3p/TRAF2 axis.Experimental and therapeutic medicine · 2023Article
- Tau pathology epigenetically remodels the neuron-glial cross-talk in Alzheimer's disease.Science advances · 2023Article
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- Dysregulated miRNAs as Biomarkers and Therapeutical Targets in Neurodegenerative Diseases.Journal of personalized medicine · 2022Review
- Estrogens still represent an attractive therapeutic approach for Alzheimer's disease.Neural regeneration research · 2022Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The two estrogen receptors (ERs), ERα and ERβ, mediate the diverse biological functions of estradiol. Opposite effects of ERα and ERβ have been found in estrogen-induced cancer cell proliferation and differentiation as well as in memory-related tasks. However, whether these opposite effects are implicated in the pathogenesis of Alzheimer's disease (AD) remains unclear. Here, we find that ERα and ERβ play contrasting roles in regulating tau phosphorylation, which is a pathological hallmark of AD. ERα increases the expression of miR-218 to suppress the protein levels of its specific target, protein tyrosine phosphatase α (PTPα). The downregulation of PTPα results in the abnormal tyrosine hyperphosphorylation of glycogen synthase kinase-3β (resulting in activation) and protein phosphatase 2A (resulting in inactivation), the major tau kinase and phosphatase. Suppressing the increased expression of miR-218 inhibits the ERα-induced tau hyperphosphorylation as well as the PTPα decline. In contrast, ERβ inhibits tau phosphorylation by limiting miR-218 levels and restoring the miR-218 levels antagonized the attenuation of tau phosphorylation by ERβ. These data reveal for the first time opposing roles for ERα and ERβ in AD pathogenesis and suggest potential therapeutic targets for AD.
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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.