ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
Anti-inflammatory Therapy With Simvastatin Improves Neuroinflammation and CNS Function in a Mouse Model of Metachromatic Leukodystrophy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 48 citations in OpenAlex.
- Effects of sulfatide on peripheral nerves in metachromatic leukodystrophy.Annals of clinical and translational neurology · 2024Trial
- Spatial-temporal lipidomics reveals dysregulated lipid metabolism in mouse brain during Alzheimer's disease progression.Journal of advanced research · 2026Article
- Pharmacological combination of simvastatin and doxorubicin reduces tumor growth and lung metastasis in triple-negative breast cancer.Frontiers in cell and developmental biology · 2026Article
- Statins in Mitigating Anticancer Treatment-Related Cardiovascular Disease.International journal of molecular sciences · 2024Review
- Dose-response evaluation of intravenous gene therapy in a symptomatic mouse model of metachromatic leukodystrophy.Molecular therapy. Methods & clinical development · 2024Article
- Olaparib Attenuates Demyelination and Neuroinflammation in an Organotypic Slice Culture Model of Metachromatic Leukodystrophy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Article
- Identification of neurodegeneration indicators and disease progression in metachromatic leukodystrophy using quantitative NMR-based urinary metabolomics.JIMD reports · 2022Article
- Existing Evidence for the Repurposing of PARP-1 Inhibitors in Rare Demyelinating Diseases.Cancers · 2022Review
- Vascularized pulp regeneration via injecting simvastatin functionalized GelMA cryogel microspheres loaded with stem cells from human exfoliated deciduous teeth.Materials today. Bio · 2022Article
- Review
- Genetic defects in the sphingolipid degradation pathway and their effects on microglia in neurodegenerative disease.Cellular signalling · 2021Review
- Complete Correction of Brain and Spinal Cord Pathology in Metachromatic Leukodystrophy Mice.Frontiers in molecular neuroscience · 2021Article
- Simvastatin Prevents Long-Term Cognitive Deficits in Sepsis Survivor Rats by Reducing Neuroinflammation and Neurodegeneration.Neurotoxicity research · 2020Article
- Comprehensive clinical, biochemical, radiological and genetic analysis of 28 Turkish cases with suspected metachromatic leukodystrophy and their relatives.Molecular genetics and metabolism reports · 2020Article
- Innate immune response in neuronopathic forms of Gaucher disease confers resistance against viral-induced encephalitis.Acta neuropathologica communications · 2020Article
- Lovastatin-mediated MCF-7 cancer cell death involves LKB1-AMPK-p38MAPK-p53-survivin signalling cascade.Journal of cellular and molecular medicine · 2020Article
- Pre-clinical Mouse Models of Neurodegenerative Lysosomal Storage Diseases.Frontiers in molecular biosciences · 2020Review
- Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches.Frontiers in medicine · 2020Review
- Comparative benefits of simvastatin and exercise in a mouse model of vascular cognitive impairment and dementia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by a functional deficiency of the lysosomal enzyme arylsulfatase A. The prevailing late-infantile variant of MLD is characterized by widespread and progressive demyelination of the central nervous system (CNS) causing death during childhood. In order to gain insight into the pathomechanism of the disease and to identify novel therapeutic targets, we analyzed neuroinflammation in two mouse models reproducing a mild, nondemyelinating, and a more severe, demyelinating, variant of MLD, respectively. Microgliosis and upregulation of cytokine/chemokine levels were clearly more pronounced in the demyelinating model. The analysis of the temporal cytokine/chemokine profiles revealed that the onset of demyelination is preceded by a sustained elevation of the macrophage inflammatory protein (MIP)-1α followed by an upregulation of MIP-1β, monocyte chemotactic protein (MCP)-1, and several interleukins. The tumor necrosis factor (TNF)-α remains unchanged. Treatment of the demyelinating mouse model with the nonsteroidal anti-inflammatory drug simvastatin reduced neuroinflammation, improved the swimming performance and ataxic gait, and retarded demyelination of the spinal cord. Our data suggest that neuroinflammation is causative for demyelination in MLD mice and that anti-inflammatory treatment might be a novel therapeutic option to improve the CNS function of MLD patients.
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