ArticleThe Journal of clinical investigation2013
Accelerated neurodegeneration through chaperone-mediated oligomerization of tau.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 195 papers, 3 of them syntheses that pooled it.
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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
195 citing papers in PubMed, 3 syntheses or guidelines pooled it, 313 citations in OpenAlex.
- Cross-tissue analysis of blood and brain epigenome-wide association studies in Alzheimer's disease.Nature communications · 2022Pooled it
- Meta-analysis of genome-wide DNA methylation identifies shared associations across neurodegenerative disorders.Genome biology · 2021Pooled it
- Epigenetic Pathways in Human Disease: The Impact of DNA Methylation on Stress-Related Pathogenesis and Current Challenges in Biomarker Development.EBioMedicine · 2017Pooled it
- Article
- Stress and glucocorticoid exposure as a critical environmental risk factor for Alzheimer's disease.Journal of neuroimmunology · 2026Article
- Dual proximity-based interactome mapping of FKBP51 and FKBP52 uncovers shared metabolic networks.Biochemical and biophysical research communications · 2026Article
- Hsp90: A means to an end.Cell stress & chaperones · 2026Review
- FKBP51: A new target for Parkinson's disease.Neural regeneration research · 2026Article
- FKBP51 inhibition by SAFit2 modulates tau pathology and cognitive deficits in PS19 mice.Alzheimer's research & therapy · 2026Article
- Integration of aged brain multi-omics reveals cross-system mechanisms underlying Alzheimer's disease heterogeneity.Cell reports · 2026Article
- FKBP5 regulates interferon signaling leading to myeloid cell activation in multiple sclerosis.Journal of neuroinflammation · 2026Article
- Heat shock proteins (Hsp70 and Hsp90) in neurodegeneration: pathogenic roles and therapeutic potential.Frontiers in aging neuroscience · 2026Review
- Beyond Inhibition: Rebalancing the Hsp90 Chaperone Network as a Therapeutic Strategy for Alzheimer's Disease.Drug design, development and therapy · 2026Review
- Rare and novel genetic variants in sporadic and familial Alzheimer's disease: insights from the first Saudi cohort.Frontiers in aging · 2026Article
- Increased HSD11β1 Expression in Human Leiomyomatous Uteri: Implication for Enhanced Glucocorticoid Signaling.The Journal of clinical endocrinology and metabolism · 2025Article
- Single-cell, multi-region profiling of the macaque brain across the lifespan.bioRxiv : the preprint server for biology · 2025Article
- Review
- FKBP5 Regulates Osteogenesis of Human iPSC-Derived Mesenchymal Stem Cells via FKBP5-AKT-FOXO1 Pathway.Journal of cellular and molecular medicine · 2025Article
- Beyond Folding: Expanding the Functional Landscape of Hsp90 Chaperone Machinery in Health and Disease.International journal of molecular sciences · 2025Review
- Network-Medicine-Guided Drug Repurposing for Alzheimer's Disease: A Multi-Dimensional Systems Pharmacology Approach.International journal of molecular sciences · 2025Article
135 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 6 institutions in 2 countries.
Funding
Abstract
Aggregation of tau protein in the brain is associated with a class of neurodegenerative diseases known as tauopathies. FK506 binding protein 51 kDa (FKBP51, encoded by FKBP5) forms a mature chaperone complex with Hsp90 that prevents tau degradation. In this study, we have shown that tau levels are reduced throughout the brains of Fkbp5-/- mice. Recombinant FKBP51 and Hsp90 synergized to block tau clearance through the proteasome, resulting in tau oligomerization. Overexpression of FKBP51 in a tau transgenic mouse model revealed that FKBP51 preserved the species of tau that have been linked to Alzheimer's disease (AD) pathogenesis, blocked amyloid formation, and decreased tangle load in the brain. Alterations in tau turnover and aggregate structure corresponded with enhanced neurotoxicity in mice. In human brains, FKBP51 levels increased relative to age and AD, corresponding with demethylation of the regulatory regions in the FKBP5 gene. We also found that higher FKBP51 levels were associated with AD progression. Our data support a model in which age-associated increases in FKBP51 levels and its interaction with Hsp90 promote neurotoxic tau accumulation. Strategies aimed at attenuating FKBP51 levels or its interaction with Hsp90 have the potential to be therapeutically relevant for AD and other tauopathies.
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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.