ArticleHuman molecular genetics2015
Neuronopathic Gaucher disease: dysregulated mRNAs and miRNAs in brain pathogenesis and effects of pharmacologic chaperone treatment in a mouse model.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Value of Glucosylsphingosine (Lyso-Gb1) as a Biomarker in Gaucher Disease: A Systematic Literature Review.International journal of molecular sciences · 2020Pooled it
- Article
- Constraint-based modelling of metabolic dysregulation in Gaucher disease: mitochondrial dysfunction and disrupted cholesterol homeostasis.Orphanet journal of rare diseases · 2026Article
- Transcriptomic signatures in Gaucher disease subtypes: A systems biology perspective.Molecular genetics and metabolism reports · 2025Article
- Central Roles of Glucosylceramide in Driving Cancer Pathogenesis.International journal of molecular sciences · 2025Review
- Glucosylsphingosine affects mitochondrial function in a neuronal cell model.Communications biology · 2025Article
- Expression Profiles of Exosomal miRNAs in Gaucher Patients and Their Association With Severity of Bone Involvement.Journal of inherited metabolic disease · 2025Article
- Current opinion on pluripotent stem cell technology in Gaucher's disease: challenges and future prospects.Cytotechnology · 2025Review
- Epigenetic landscape in lysosomal storage disorders: mechanisms and modulation.Frontiers in genetics · 2025Review
- Biomarkers for gene therapy clinical trials of lysosomal storage disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Therapeutic Role of Pharmacological Chaperones in Lysosomal Storage Disorders: A Review of the Evidence and Informed Approach to Reclassification.Biomolecules · 2023Review
- iPSC-derived neural precursor cells engineeringMolecular therapy. Methods & clinical development · 2023Article
- Exploring Pro-Inflammatory Immunological Mediators: Unraveling the Mechanisms of Neuroinflammation in Lysosomal Storage Diseases.Biomedicines · 2023Review
- The landscape of CRISPR/Cas9 for inborn errors of metabolism.Molecular genetics and metabolism · 2023Review
- Targeting the Complement-Sphingolipid System in COVID-19 and Gaucher Diseases: Evidence for a New Treatment Strategy.International journal of molecular sciences · 2022Review
- Review
- Secondary Mitochondrial Dysfunction as a Cause of Neurodegenerative Dysfunction in Lysosomal Storage Diseases and an Overview of Potential Therapies.International journal of molecular sciences · 2022Review
- Establishment and Phenotypic Analysis of the Novel Gaucher Disease Mouse Model With the Partially HumanizedFrontiers in genetics · 2022Article
- Neuronopathic Gaucher disease: Beyond lysosomal dysfunction.Frontiers in molecular neuroscience · 2022Review
- A multifaceted evaluation of microgliosis and differential cellular dysregulation of mammalian target of rapamycin signaling in neuronopathic Gaucher disease.Frontiers in molecular neuroscience · 2022Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Defective lysosomal acid β-glucosidase (GCase) in Gaucher disease causes accumulation of glucosylceramide (GC) and glucosylsphingosine (GS) that distress cellular functions. To study novel pathological mechanisms in neuronopathic Gaucher disease (nGD), a mouse model (4L;C*), an analogue to subacute human nGD, was investigated for global profiles of differentially expressed brain mRNAs (DEGs) and miRNAs (DEmiRs). 4L;C* mice displayed accumulation of GC and GS, activated microglial cells, reduced number of neurons and aberrant mitochondrial function in the brain followed by deterioration in motor function. DEGs and DEmiRs were characterized from sequencing of mRNA and miRNA from cerebral cortex, brain stem, midbrain and cerebellum of 4L;C* mice. Gene ontology enrichment and pathway analysis showed preferential mitochondrial dysfunction in midbrain and uniform inflammatory response and identified novel pathways, axonal guidance signaling, synaptic transmission, eIF2 and mammalian target of rapamycin (mTOR) signaling potentially involved in nGD. Similar analyses were performed with mice treated with isofagomine (IFG), a pharmacologic chaperone for GCase. IFG treatment did not alter the GS and GC accumulation significantly but attenuated the progression of the disease and altered numerous DEmiRs and target DEGs to their respective normal levels in inflammation, mitochondrial function and axonal guidance pathways, suggesting its regulation on miRNA and the associated mRNA that underlie the neurodegeneration in nGD. These analyses demonstrate that the neurodegenerative phenotype in 4L;C* mice was associated with dysregulation of brain mRNAs and miRNAs in axonal guidance, synaptic plasticity, mitochondria function, eIF2 and mTOR signaling and inflammation and provides new insights for the nGD pathological mechanism.
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Registered trials
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