ArticlePloS one2017
Protamine neutralizes chondroitin sulfate proteoglycan-mediated inhibition of oligodendrocyte differentiation.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- A dual role for pleiotrophin in modulating inflammation and myelination in the presence of chondroitin sulfate proteoglycans after nervous system injury.Frontiers in cellular neuroscience · 2025Article
- Chondroitin Sulfate Proteoglycans Revisited: Its Mechanism of Generation and Action for Spinal Cord Injury.Aging and disease · 2024Review
- In vitro assessment of protamine toxicity with neural cells, its therapeutic potential to counter chondroitin sulfate mediated neuron inhibition, and its effects on reactive astrocytes.Advanced therapeutics · 2024Article
- ADAMTS4 Enhances Oligodendrocyte Differentiation and Remyelination by Cleaving NG2 Proteoglycan and AttenuatingThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Remyelination in Multiple Sclerosis: Findings in the Cuprizone Model.International journal of molecular sciences · 2022Review
- The Role of Extracellular Matrix in Human Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- Oligodendrocyte and Extracellular Matrix Contributions to Central Nervous System Motor Function: Implications for Dystonia.Movement disorders : official journal of the Movement Disorder Society · 2022Review
- Low-Molecular Weight Protamine Overcomes Chondroitin Sulfate Inhibition of Neural Regeneration.Frontiers in cell and developmental biology · 2022Article
- Heparan sulfate proteoglycans serve as alternative receptors for low affinity LCMV variants.PLoS pathogens · 2021Article
- THAP1 modulates oligodendrocyte maturation by regulating ECM degradation in lysosomes.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Interaction between Neurons and the Oligodendroglial Lineage in Multiple Sclerosis and Its Preclinical Models.Life (Basel, Switzerland) · 2021Review
- Dynamics of Central Remyelination and Treatment Evolution in a Model of Multiple Sclerosis with Optic Coherence Tomography.International journal of molecular sciences · 2021Article
- Premyelinating Oligodendrocytes: Mechanisms Underlying Cell Survival and Integration.Frontiers in cell and developmental biology · 2021Review
- The glycosyltransferase EXTL2 promotes proteoglycan deposition and injurious neuroinflammation following demyelination.Journal of neuroinflammation · 2020Article
- Regulation of autophagy by inhibitory CSPG interactions with receptor PTPσ and its impact on plasticity and regeneration after spinal cord injury.Experimental neurology · 2020Review
- Regulation of Oligodendrocyte Functions: Targeting Lipid Metabolism and Extracellular Matrix for Myelin Repair.Journal of clinical medicine · 2020Review
- The Association between Genes Polymorphisms of Heparan Sulfate Proteoglycan 2 (Iranian journal of public health · 2019Review
- The Expression, Functions, Interactions and Prognostic Values of PTPRZ1: A Review and Bioinformatic Analysis.Journal of Cancer · 2019Review
- The Extracellular Environment of the CNS: Influence on Plasticity, Sprouting, and Axonal Regeneration after Spinal Cord Injury.Neural plasticity · 2018Review
- Cspg4 sculpts oligodendrocyte precursor cell morphology.Differentiation; research in biological diversityArticle
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chondroitin sulfate proteoglycans (CSPGs), which are enriched in demyelinating plaques in neurodegenerative diseases, such as multiple sclerosis (MS), impair remyelination by inhibiting the migration and differentiation of oligodendrocyte precursor cells (OPCs) in the central nervous system (CNS). We herein show that protamine (PRM, also known as a heparin antagonist) effectively neutralizes the inhibitory activities of CSPGs, thereby enhancing OPC differentiation and (re)myelination in mice. Cell-based assays using mouse OPC-like OL1 cells revealed that the PRM treatment exerted masking effects on extracellular CSPGs and improved oligodendrocyte differentiation on inhibitory CSPG-coated substrates. PRM also bound to the extracellular region of protein tyrosine phosphatase receptor type Z (PTPRZ), a membrane-spanning CSPG predominantly expressed in OPCs, and functioned as a ligand mimetic of PTPRZ, thereby suppressing its negative regulatory activity on oligodendrocyte differentiation. In primary cultures, the differentiation of OPCs from wild-type and Ptprz-deficient mice was equally enhanced by PRM. Moreover, the intranasal administration of PRM accelerated myelination in the developing mouse brain, and its intracerebroventricular administration stimulated remyelination after cuprizone-induced demyelination. These results indicate that PRM has CSPG-neutralizing activity which promotes oligodendrocyte differentiation under developmental and morbid conditions.
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