ArticleAnesthesiology2020
Dantrolene Ameliorates Impaired Neurogenesis and Synaptogenesis in Induced Pluripotent Stem Cell Lines Derived from Patients with Alzheimer's Disease.
Article in Anesthesiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 30 citations in OpenAlex.
- Advancements in differentiation of induced pluripotent stem cells into specialized neuronal subtypes.Neural regeneration research · 2026Article
- Screening of cell-type-specific meta-programs for drug repurposing in Alzheimer's disease.Briefings in bioinformatics · 2026Article
- Intranasal dantrolene nanoparticles inhibit lipopolysaccharide-induced depression and anxiety behavior in mice.Translational psychiatry · 2026Article
- Crystal structures of Ryanodine Receptor reveal dantrolene and azumolene interactions guiding inhibitor development.Nature communications · 2025Article
- Dantrolene Protects Hippocampal Neurons Against Amyloid-β₁₋₄₂-Induced Calcium Dysregulation and Cell Death.Neurochemical research · 2025Article
- Intranasal Dantrolene Nanoparticles for Treatment of Amyotrophic Lateral Sclerosis as a Disease-Modifying Drug.bioRxiv : the preprint server for biology · 2025Article
- Intranasal Delivery of Lithium Salt Suppresses Inflammatory Pyroptosis in the Brain and Ameliorates Memory Loss and Depression-like Behavior in 5XFAD Mice.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Intranasal Delivery of Lithium Salt Suppresses Inflammatory Pyroptosis in the brain and Ameliorates Memory Loss and Depression-like Behavior in 5XFAD mice.bioRxiv : the preprint server for biology · 2024Article
- Replacing Animal Testing with Stem Cell-Organoids : Advantages and Limitations.Stem cell reviews and reports · 2024Review
- Neuroprotective effects of dantrolene in neurodegenerative disease: Role of inhibition of pathological inflammation.Journal of anesthesia and translational medicine · 2024Article
- TFR1 knockdown alleviates iron overload and mitochondrial dysfunction during neural differentiation of Alzheimer's disease-derived induced pluripotent stem cells by interacting with GSK3B.European journal of medical research · 2024Article
- Effects of Intranasal Dantrolene Nanoparticles on Brain Concentration and Behavior in PS19 Tau Transgenic Mice.Journal of Alzheimer's disease : JAD · 2024Article
- Cytosolic calcium: Judge, jury and executioner of neurodegeneration in Alzheimer's disease and beyond.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Review
- Current clinical application of dantrolene sodium.Anesthesia and pain medicine · 2023Review
- Role of Calcium Modulation in the Pathophysiology and Treatment of Alzheimer's Disease.International journal of molecular sciences · 2023Review
- The Breakthroughs and Caveats of Using Human Pluripotent Stem Cells in Modeling Alzheimer's Disease.Cells · 2023Review
- Protein mishandling and impaired lysosomal proteolysis generated through calcium dysregulation in Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Potential mechanisms underlying lithium treatment for Alzheimer's disease and COVID-19.European review for medical and pharmacological sciences · 2022Review
- Review
- Dantrolene repurposed to treat sepsis or septic shock and COVID-19 patients.European review for medical and pharmacological sciences · 2021Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundOveractivation of ryanodine receptors and the resulting impaired calcium homeostasis contribute to Alzheimer's disease-related pathophysiology. This study hypothesized that exposing neuronal progenitors derived from induced pluripotent stems cells of patients with Alzheimer's disease to dantrolene will increase survival, proliferation, neurogenesis, and synaptogenesis.
methodsInduced pluripotent stem cells obtained from skin fibroblast of healthy subjects and patients with familial and sporadic Alzheimer's disease were used. Biochemical and immunohistochemical methods were applied to determine the effects of dantrolene on the viability, proliferation, differentiation, and calcium dynamics of these cells.
resultsDantrolene promoted cell viability and proliferation in these two cell lines. Compared with the control, differentiation into basal forebrain cholinergic neurons significantly decreased by 10.7% (32.9 ± 3.6% vs. 22.2 ± 2.6%, N = 5, P = 0.004) and 9.2% (32.9 ± 3.6% vs. 23.7 ± 3.1%, N = 5, P = 0.017) in cell lines from sporadic and familial Alzheimer's patients, respectively, which were abolished by dantrolene. Synapse density was significantly decreased in cortical neurons generated from stem cells of sporadic Alzheimer's disease by 58.2% (237.0 ± 28.4 vs. 99.0 ± 16.6 arbitrary units, N = 4, P = 0.001) or familial Alzheimer's disease by 52.3% (237.0 ± 28.4 vs.113.0 ± 34.9 vs. arbitrary units, N = 5, P = 0.001), which was inhibited by dantrolene in the familial cell line. Compared with the control, adenosine triphosphate (30 µM) significantly increased higher peak elevation of cytosolic calcium concentrations in the cell line from sporadic Alzheimer's patients (84.1 ± 27.0% vs. 140.4 ± 40.2%, N = 5, P = 0.049), which was abolished by the pretreatment of dantrolene. Dantrolene inhibited the decrease of lysosomal vacuolar-type H-ATPase and the impairment of autophagy activity in these two cell lines from Alzheimer's disease patients.
conclusionsDantrolene ameliorated the impairment of neurogenesis and synaptogenesis, in association with restoring intracellular Ca homeostasis and physiologic autophagy, cell survival, and proliferation in induced pluripotent stem cells and their derived neurons from sporadic and familial Alzheimer's disease patients.
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