ArticleCell death & disease2016
Glial degeneration with oxidative damage drives neuronal demise in MPSII disease.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
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- Enzyme replacement with transferrin receptor-targeted α-L-iduronidase rescues brain pathology in mucopolysaccharidosis I mice.Molecular therapy. Methods & clinical development · 2023Article
- Mucopolysaccharidosis: What Pediatric Rheumatologists and Orthopedics Need to Know.Diagnostics (Basel, Switzerland) · 2022Review
- Rag2Stem cell reports · 2022Article
- Azithromycin Protects Retinal Glia Against Oxidative Stress-Induced Morphological Changes, Inflammation, and Cell Death.ACS bio & med chem Au · 2022Article
- Pathogenic Roles of Heparan Sulfate and Its Use as a Biomarker in Mucopolysaccharidoses.International journal of molecular sciences · 2022Review
- Lysosomal positioning diseases: beyond substrate storage.Open biology · 2022Review
- 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
- Dose-dependent effects of a brain-penetrating iduronate-2-sulfatase on neurobehavioral impairments in mucopolysaccharidosis II mice.Molecular therapy. Methods & clinical development · 2022Article
- Innate Immunity in Mucopolysaccharide Diseases.International journal of molecular sciences · 2022Review
- Enzyme Replacement Therapy with Pabinafusp Alfa for Neuronopathic Mucopolysaccharidosis II: An Integrated Analysis of Preclinical and Clinical Data.International journal of molecular sciences · 2021Article
- Oxidative Stress in Mucopolysaccharidoses: Pharmacological Implications.Molecules (Basel, Switzerland) · 2021Review
- Clearance of heparan sulfate in the brain prevents neurodegeneration and neurocognitive impairment in MPS II mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Can serial cerebral MRIs predict the neuronopathic phenotype of MPS II?Journal of inherited metabolic disease · 2021Article
- The rapidly evolving view of lysosomal storage diseases.EMBO molecular medicine · 2021Review
- Modeling Mucopolysaccharidosis Type II in the Fruit Fly by Using the RNA Interference Approach.Life (Basel, Switzerland) · 2020Article
- Reactive Oxygen Species and Oxidative Stress in the Pathogenesis and Progression of Genetic Diseases of the Connective Tissue.Antioxidants (Basel, Switzerland) · 2020Review
- Evidence for inflammasome activation in the brain of mucopolysaccharidosis type II mice.Metabolic brain disease · 2020Article
- Neural Stem Cells from Shank3-ko Mouse Model Autism Spectrum Disorders.Molecular neurobiology · 2020Article
- Mucopolysaccharidosis Type II: One Hundred Years of Research, Diagnosis, and Treatment.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mucopolysaccharidosis type II (MPSII) is a lysosomal storage disorder due to the deficit of the iduronate 2-sulfatase (IDS) enzyme, causing progressive neurodegeneration in patients. Neural stem cells (NSCs) derived from the IDS-ko mouse can recapitulate MPSII pathogenesis in vitro. In differentiating IDS-ko NSCs and in the aging IDS-ko mouse brain, glial degeneration precedes neuronal degeneration. Here we show that pure IDS-ko NSC-derived astrocytes are selectively able to drive neuronal degeneration when cocultured with healthy neurons. This phenotype suggests concurrent oxidative damage with metabolic dysfunction. Similar patterns were observed in murine IDS-ko animals and in human MPSII brains. Most importantly, the mutant phenotype of IDS-ko astrocytes was reversed by low oxygen conditions and treatment with vitamin E, which also reversed the toxic effect on cocultured neurons. Moreover, at very early stages of disease we detected in vivo the development of a neuroinflammatory background that precedes astroglial degeneration, thus suggesting a novel model of MPSII pathogenesis, with neuroinflammation preceding glial degeneration, which is finally followed by neuronal death. This hypothesis is also consistent with the progression of white matter abnormalities in MPSII patients. Our study represents a novel breakthrough in the elucidation of MPSII brain pathogenesis and suggests the antioxidant molecules as potential therapeutic tools to delay MPSII onset and progression.
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