The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Hyaluronan blocks oligodendrocyte progenitor maturation and remyelination through TLR2
Open accessAbstract
Failure of remyelination is largely responsible for sustained neurologic symptoms in multiple sclerosis (MS). MS lesions contain hyaluronan deposits that inhibit oligodendrocyte precursor cell (OPC) maturation. However, the mechanism behind this inhibition is unclear. We report here that Toll-like receptor 2 (TLR2) is expressed by oligodendrocytes and is up-regulated in MS lesions. Pathogen-derived TLR2 agonists, but not agonists for other TLRs, inhibit OPC maturation in vitro. Hyaluronan-mediated inhibition of OPC maturation requires TLR2 and MyD88, a TLR2 adaptor molecule. Ablated expression of TLR2 also enhances remyelination in a lysolecithin animal model. Hyaluronidases expressed by OPCs degrade hyaluronan to hyaluronan oligomers, a requirement for hyaluronan/TLR2 signaling. MS lesions contain both TLR2 + oligodendrocytes and low-molecular-weight hyaluronan, consistent with their importance to remyelination in MS. We thus have defined a mechanism controlling remyelination failure in MS where hyaluronan is degraded by hyaluronidases into hyaluronan oligomers that block OPC maturation and remyelination through TLR2-MyD88 signaling.
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Cites
Regulation of lung injury and repair by Toll-like receptors and hyaluronan
Jiang, D., Liang, J., Fan, J., Yu, S., Chen, S., Luo, Y., Prestwich, G. D., Mascarenhas, M. M., Garg, H. G., Quinn, D. A., et al. (2005) · Nature Medicine · doi:10.1038/nm1315 · Cited by 1,401
Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4
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Self-citationPremyelinating Oligodendrocytes in Chronic Lesions of Multiple Sclerosis
Chang, A., Tourtellotte, W. W., Rudick, R., & Trapp, B. D. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa010994 · Cited by 991
Self-citationHyaluronan Fragments Act as an Endogenous Danger Signal by Engaging TLR2
Scheibner, K. A., Lutz, M. A., Boodoo, S., Fenton, M. J., Powell, J. D., & Horton, M. R. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.2.1272 · Cited by 708
Hyaluronan accumulates in demyelinated lesions and inhibits oligodendrocyte progenitor maturation
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bHLH Transcription Factor Olig1 Is Required to Repair Demyelinated Lesions in the CNS
Arnett, H. A., Fancy, S. P. J., Alberta, J. A., Zhao, C., Plant, S. R., Kaing, S., Raine, C. S., Rowitch, D. H., Franklin, R. J. M., & Stiles, C. D. (2004) · Science · doi:10.1126/science.1103709 · Cited by 416
Cited by
Lassmann, H. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a028936 · Cited by 937
Regenerating CNS myelin — from mechanisms to experimental medicines
Franklin, R. J. M., & ffrench-Constant, C. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.136 · Cited by 647
Pattern recognition receptors and central nervous system repair
Kigerl, K. A., de Rivero Vaccari, J. P., Dietrich, W. D., Popovich, P. G., & Keane, R. W. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2014.01.001 · Cited by 490
White matter injury in the preterm infant: pathology and mechanisms
Back, S. A. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1718-6 · Cited by 473
Oligodendrocyte‐microglia cross‐talk in the central nervous system
Peferoen, L., Kipp, M., van der Valk, P., van Noort, J. M., & Amor, S. (2014) · Immunology · doi:10.1111/imm.12163 · Cited by 438
Metadata
- Authors
- Sloane, J. A., Batt, C., Ma, Y., Harris, Z. M., Trapp, B., & Vartanian, T.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2010-06-03
- Volume
- 107
- Issue
- 25
- Pages
- 11555-11560
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2077702475
- Cited by
- 360
- References
- 8
- FWCI
- 14.81
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Hyaluronan blocks oligodendrocyte progenitor maturation and remyelination through TLR2. https://app.cochat.ai/papers/10.1073/pnas.1006496107
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- Sloane, J. A., Batt, C., Ma, Y., Harris, Z. M., Trapp, B., & Vartanian, T. (2010). Hyaluronan blocks oligodendrocyte progenitor maturation and remyelination through TLR2. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1006496107
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