ArticleBrain : a journal of neurology2023
Glucocorticoid-driven mitochondrial damage stimulates Tau pathology.
Article in Brain : a journal of neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
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
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Restoring Gut-brain Function by Medicinal Herbs Offering Neuroprotection through Suppressing Inflammatory Pathways: A Systematic Review.Current neuropharmacology · 2025Pooled it
- Tau protein as a regulator of mitochondrial function and dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- NR3C1/PRKACG-mediated impairment of mitochondrial quality control underlies stress-induced hypothalamic neuronal injury.Communications biology · 2026Article
- Tracheal aspirates of mechanically ventilated preterm infants possess cytopathic tau variants: a prospective exploratory study.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- APOE4 exacerbates glucocorticoid stress hormone-induced tau pathology via mitochondrial dysfunction.Cell death & disease · 2026Article
- Astrocyte Bioenergetic Remodeling as a Central Trait of Disrupted Glucocorticoid Signaling: Mechanisms and Implications for Stress Vulnerability.Journal of neurochemistry · 2026Review
- Genetic Deletion of Cyclophilin D Results in Enhanced Hypoxia Tolerance in Mice.Cellular and molecular neurobiology · 2026Article
- Role for NF-κB in herpes encephalitis pathology in mice genocopying an inborn error of IRF3-IFN immunity.The Journal of experimental medicine · 2026Article
- From Early Adversity to Neurodegeneration: Stress Biomarkers as Predictive Signals for Lifespan Brain Health.International journal of molecular sciences · 2025Review
- RNA Granules at the Crossroads of Synaptic Dysfunction and Neurodegeneration.Journal of neurochemistry · 2025Review
- Glucocorticoids regulate small extracellular vesicle (sEV) release via activation of nSMase2.bioRxiv : the preprint server for biology · 2025Article
- Multiscale Organization of Neural Networks in a 3D Bioprinted Matrix.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Decoding the role of glucocorticoid-regulated kinase 1 in Alzheimer's disease: a promising path toward novel therapeutic strategies.Inflammopharmacology · 2025Review
- Vitamin KDrug design, development and therapy · 2025Article
- Mitochondrial Functioning: Front and Center in Defining Psychosomatic Mechanisms of Allostasis in Health and Disease.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Identification of JAZF1, KNOP1, and PLEKHA1 as causally associated genes and drug targets for Alzheimer's disease: a summary data-based Mendelian randomization study.Inflammopharmacology · 2024Article
- Pharmacology, medical uses, and clinical translational challenges of Saikosaponin A: A review.Heliyon · 2024Review
- The multiple roles of chronic stress and glucocorticoids in Alzheimer's disease pathogenesis.Trends in neurosciences · 2024Review
- Delocalized quinolinium-macrocyclic peptides, an atypical chemotype for CNS penetration.Science advances · 2024Article
- Experimental laboratory models as tools for understanding modifiable dementia risk.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Prolonged exposure to glucocorticoids, the main stress hormones, damages the brain and is a risk factor for depression and Alzheimer's disease. Two major drivers of glucocorticoid-related neurotoxicity are mitochondrial dysfunction and Tau pathology; however, the molecular/cellular mechanisms precipitating these events, and their causal relationship, remain unclear. Using cultured murine hippocampal neurons and 4-5-month-old mice treated with the synthetic glucocorticoid dexamethasone, we investigate the mechanisms underlying glucocorticoid-induced mitochondrial damage and Tau pathology. We find that glucocorticoids stimulate opening of the mitochondrial permeability transition pore via transcriptional upregulation of its activating component, cyclophilin D. Inhibition of cyclophilin D is protective against glucocorticoid-induced mitochondrial damage as well as Tau phosphorylation and oligomerization in cultured neurons. We further identify the mitochondrially-targeted compound mito-apocynin as an inhibitor of glucocorticoid-induced permeability transition pore opening, and show that this compound protects against mitochondrial dysfunction, Tau pathology, synaptic loss, and behavioural deficits induced by glucocorticoids in vivo. Finally, we demonstrate that mito-apocynin and the glucocorticoid receptor antagonist mifepristone rescue Tau pathology in cytoplasmic hybrid cells, an ex vivo Alzheimer's disease model wherein endogenous mitochondria are replaced with mitochondria from Alzheimer's subjects. These findings show that mitochondrial permeability transition pore opening is a precipitating factor in glucocorticoid-induced mitochondrial dysfunction, and that this event stimulates Tau pathogenesis. Our data also link glucocorticoids to mitochondrial dysfunction and Tau pathology in the context of Alzheimer's disease and suggest that mitochondria are promising therapeutic targets for mitigating stress- and Tau-related brain damage.
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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.