ArticleHuman molecular genetics2016
Modulating ryanodine receptors with dantrolene attenuates neuronopathic phenotype in Gaucher disease mice.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 34 citations in OpenAlex.
- Suppression of Glucosylceramide Synthase Reverses Drug Resistance in Cancer Cells Harboring Homozygous p53 Mutants.International journal of molecular sciences · 2026Article
- Dantrolene Protects Hippocampal Neurons Against Amyloid-β₁₋₄₂-Induced Calcium Dysregulation and Cell Death.Neurochemical research · 2025Article
- Article
- N-acetylcysteine Pharmacology and Applications in Rare Diseases-Repurposing an Old Antioxidant.Antioxidants (Basel, Switzerland) · 2023Review
- iPSC-derived neural precursor cells engineeringMolecular therapy. Methods & clinical development · 2023Article
- Cure of Alzheimer's Dementia Requires Addressing All of the Affected Brain Cell Types.Journal of clinical medicine · 2023Article
- Formulating treatment of major psychiatric disorders: algorithm targets the dominantly affected brain cell-types.Discover mental health · 2023Review
- Neuroinflammation in Gaucher disease, neuronal ceroid lipofuscinosis, and commonalities with Parkinson's disease.Brain research · 2022Review
- Gaucher disease - more than just a rare lipid storage disease.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Ion Channels and Transporters in Autophagy.Autophagy · 2022Article
- Article
- Dantrolene repurposed to treat sepsis or septic shock and COVID-19 patients.European review for medical and pharmacological sciences · 2021Review
- How Is the Fidelity of Proteins Ensured in Terms of Both Quality and Quantity at the Endoplasmic Reticulum? Mechanistic Insights into E3 Ubiquitin Ligases.International journal of molecular sciences · 2021Review
- Endoplasmic Reticulum-Based Calcium Dysfunctions in Synucleinopathies.Frontiers in neurology · 2021Review
- Calcium Ions Aggravate Alzheimer's Disease Through the Aberrant Activation of Neuronal Networks, Leading to Synaptic and Cognitive Deficits.Frontiers in molecular neuroscience · 2021Review
- Gb3-cSrc complex in glycosphingolipid-enriched microdomains contributes to the expression of p53 mutant protein and cancer drug resistance via β-catenin-activated RNA methylation.FASEB bioAdvances · 2020Article
- Systemic enzyme delivery by blood-brain barrier-penetrating SapC-DOPS nanovesicles for treatment of neuronopathic Gaucher disease.EBioMedicine · 2020Article
- Pre-clinical Mouse Models of Neurodegenerative Lysosomal Storage Diseases.Frontiers in molecular biosciences · 2020Review
- mTOR hyperactivity mediates lysosomal dysfunction in Gaucher's disease iPSC-neuronal cells.Disease models & mechanisms · 2019Article
- Intravenous infusion of iPSC-derived neural precursor cells increases acid β-glucosidase function in the brain and lessens the neuronopathic phenotype in a mouse model of Gaucher disease.Human molecular genetics · 2019Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Neuronopathic Gaucher disease (nGD) manifests as severe neurological symptoms in patients with no effective treatment available. Ryanodine receptors (Ryrs) are a family of calcium release channels on intracellular stores. The goal of this study is to determine if Ryrs are potential targets for nGD treatment. A nGD cell model (CBE-N2a) was created by inhibiting acid β-glucosidase (GCase) in N2a cells with conduritol B epoxide (CBE). Enhanced cytosolic calcium in CBE-N2a cells was blocked by either ryanodine or dantrolene, antagonists of Ryrs and by Genz-161, a glucosylceramide synthase inhibitor, suggesting substrate-mediated ER-calcium efflux occurs through ryanodine receptors. In the brain of a nGD (4L;C*) mouse model, expression of Ryrs was normal at 13 days of age, but significantly decreased below the wild type level in end-stage 4L;C* brains at 40 days. Treatment with dantrolene in 4L;C* mice starting at postnatal day 5 delayed neurological pathology and prolonged survival. Compared to untreated 4L;C* mice, dantrolene treatment significantly improved gait, reduced LC3-II levels, improved mitochondrial ATP production and reduced inflammation in the brain. Dantrolene treatment partially normalized Ryr expression and its potential regulators, CAMK IV and calmodulin. Furthermore, dantrolene treatment increased residual mutant GCase activity in 4L;C* brains. These data demonstrate that modulating Ryrs has neuroprotective effects in nGD through mechanisms that protect the mitochondria, autophagy, Ryr expression and enhance GCase activity. This study suggests that calcium signalling stabilization, e.g. with dantrolene, could be a potential disease modifying therapy for nGD.
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