ArticlePloS one2009
Matrix metalloproteinase proteolysis of the myelin basic protein isoforms is a source of immunogenic peptides in autoimmune multiple sclerosis.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 89 citations in OpenAlex.
- Matrix metalloprotease-9 modulates microglial/macrophage responses in murine brain demyelination.Acta neuropathologica communications · 2026Article
- Maternal Infection Impairs Motor Coordination in an Experimental Meningitis Rat Model Through Altered MMP-2/3/9 Activity, H3K4 Trimethylation, andInternational journal of molecular sciences · 2026Article
- Transition of CELF2 PAS usage promotes recovery of refractory JDM through alternative splicing regulation of CTSB.Molecular therapy. Nucleic acids · 2025Article
- Emerging Role of Oligodendrocytes Malfunction in the Progression of Alzheimer's Disease.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Review
- Membrane-Type 5 Matrix Metalloproteinase (MT5-MMP): Background and Proposed Roles in Normal Physiology and Disease.Biomolecules · 2025Review
- New Insight into the Possible Roles of L-Carnitine in a Rat Model of Multiple Sclerosis.Brain sciences · 2023Article
- Vanillic Acid Ameliorates Demyelination in a Cuprizone-Induced Multiple Sclerosis Rat Model: Possible Underlying Mechanisms.Brain sciences · 2023Article
- The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases.International journal of molecular sciences · 2020Review
- Repurposing of Secukinumab as Neuroprotective in Cuprizone-Induced Multiple Sclerosis Experimental Model via Inhibition of Oxidative, Inflammatory, and Neurodegenerative Signaling.Molecular neurobiology · 2020Article
- Predictive models of protease specificity based on quantitative protease-activity profiling data.Biochimica et biophysica acta. Proteins and proteomics · 2019Article
- Matrix metalloproteinases in the CNS: interferons get nervous.Cellular and molecular life sciences : CMLS · 2019Review
- A sensitive and selective ELISA methodology quantifies a demyelination marker in experimental and clinical samples.Journal of immunological methods · 2018Article
- Article
- Galectin-3-Mediated Glial Crosstalk Drives Oligodendrocyte Differentiation and (Re)myelination.Frontiers in cellular neuroscience · 2018Review
- Matrix metalloproteinases - From the cleavage data to the prediction tools and beyond.Biochimica et biophysica acta. Molecular cell research · 2017Review
- Article
- Matrix metalloproteinase activity stimulates N-cadherin shedding and the soluble N-cadherin ectodomain promotes classical microglial activation.Journal of neuroinflammation · 2017Article
- Reciprocal relationship between membrane type 1 matrix metalloproteinase and the algesic peptides of myelin basic protein contributes to chronic neuropathic pain.Brain, behavior, and immunity · 2017Article
- Selective function-blocking monoclonal human antibody highlights the important role of membrane type-1 matrix metalloproteinase (MT1-MMP) in metastasis.Oncotarget · 2017Article
- Changes of gene expression in T lymphocytes following Golli‑MBP gene RNA interference.Molecular medicine reports · 2016Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMatrix metalloproteinases (MMPs) play a significant role in the fragmentation of myelin basic protein (MBP) and demyelination leading to autoimmune multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). The classic MBP isoforms are predominantly expressed in the oligodendrocytes of the CNS. The splice variants of the single MBP gene (Golli-MBP BG21 and J37) are widely expressed in the neurons and also in the immune cells. The relative contribution of the individual MMPs to the MBP cleavage is not known. METHODOLOGY/PRINCIPAL
findingsTo elucidate which MMP plays the primary role in cleaving MBP, we determined the efficiency of MMP-2, MMP-8, MMP-9, MMP-10, MMP-12, MT1-MMP, MT2-MMP, MT3-MMP, MT4-MMP, MT5-MMP and MT6-MMP in the cleavage of the MBP, BG21 and J37 isoforms in the in vitro cleavage reactions followed by mass-spectroscopy analysis of the cleavage fragments. As a result, we identified the MMP cleavage sites and the sequence of the resulting fragments. We determined that MBP, BG21 and J37 are highly sensitive to redundant MMP proteolysis. MT6-MMP (initially called leukolysin), however, was superior over all of the other MMPs in cleaving the MBP isoforms. Using the mixed lymphocyte culture assay, we demonstrated that MT6-MMP proteolysis of the MBP isoforms readily generated, with a near quantitative yield, the immunogenic N-terminal 1-15 MBP peptide. This peptide selectively stimulated the proliferation of the PGPR7.5 T cell clone isolated from mice with EAE and specific for the 1-15 MBP fragment presented in the MHC H-2(U) context. CONCLUSIONS/SIGNIFICANCE: In sum, our biochemical observations led us to hypothesize that MT6-MMP, which is activated by furin and associated with the lipid rafts, plays an important role in MS pathology and that MT6-MMP is a novel and promising drug target in MS especially when compared with other individual MMPs.
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