Cited by 612Multiple Sclerosis Research StudiesProteoglycans and glycosaminoglycans researchNeurogenesis and neuroplasticity mechanisms

Hyaluronan accumulates in demyelinated lesions and inhibits oligodendrocyte progenitor maturation

Back, Stephen A, Tuohy, Therese M F, Chen, Hanqin, Wallingford, Nicholas, Craig, Andrew, Struve, Jaime, Luo, Ning Ling, Banine, Fatima +6 more·2005·Nature Medicine

Abstract

Demyelination is the hallmark of numerous neurodegenerative conditions, including multiple sclerosis. Oligodendrocyte progenitors (OPCs), which normally mature into myelin-forming oligodendrocytes, are typically present around demyelinated lesions but do not remyelinate affected axons. Here, we find that the glycosaminoglycan hyaluronan accumulates in demyelinated lesions from individuals with multiple sclerosis and in mice with experimental autoimmune encephalomyelitis. A high molecular weight (HMW) form of hyaluronan synthesized by astrocytes accumulates in chronic demyelinated lesions. This form of hyaluronan inhibits remyelination after lysolecithin-induced white matter demyelination. OPCs accrue and do not mature into myelin-forming cells in demyelinating lesions where HMW hyaluronan is present. Furthermore, the addition of HMW hyaluronan to OPC cultures reversibly inhibits progenitor-cell maturation, whereas degrading hyaluronan in astrocyte-OPC cocultures promotes oligodendrocyte maturation. HMW hyaluronan may therefore contribute substantially to remyelination failure by preventing the maturation of OPCs that are recruited to demyelinating lesions.

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Crossref · 10.1038/nm1279

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  • The inability to phagocytose myelin debris in the cuprizone model obstructs aspects of oligodendrocyte biology, including differentiation of OPCs into myelin-producing oligodendrocytes.

    “The inability to phagocytose myelin debris in the cuprizone model is known to obstruct aspects of oligodendrocyte biology, including the differentiation of oligodendrocyte precursor cells (OPCs) into myelin-producing oligodendrocytes (Back et al., 2005).”

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Authors
Back, S. A., Tuohy, T. M. F., Chen, H., Wallingford, N., Craig, A., Struve, J., Luo, N. L., Banine, F., Liu, Y., Chang, A., Trapp, B. D., Bebo, Rao, M. S., & Sherman, L. S.
Affiliations
  • Oregon Health & Science University (US)
  • Oregon National Primate Research Center (US)
  • National Institutes of Health (US)
  • Cleveland Clinic (US)
Corresponding author
Sherman, Larry S
Venue
Nature Medicine
Published
2005-08-07
Volume
11
Issue
9
Pages
966-972
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
OpenAlex
W2108005154
Cited by
612
References
46
Citations by year
2026: 20 · 2025: 16 · 2024: 33 · 2023: 17 · 2022: 32 · 2021: 31 · 2020: 39 · 2019: 41 · 2018: 33 · 2017: 49 · 2016: 24 · 2015: 33 · 2014: 34 · 2013: 46 · 2012: 30
FWCI
11.59
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (7r01ns039550-04)
  • National Institute of Neurological Disorders and Stroke (NS 39550)
  • National Center for Research Resources (RR-00163.)
  • National Center for Complementary and Integrative Health (AT001517, R01AT001517)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
hyaluronic acid, demyelination, oligodendrocyte precursor cells, remyelination, oligodendrocyte maturation, multiple sclerosis, experimental autoimmune encephalomyelitis, astrocytes, high molecular weight hyaluronic acid, glycosaminoglycans, white matter demyelination, lysolecithin-induced demyelination
MeSH terms
Animals, Astrocytes, Demyelinating Diseases, Encephalomyelitis, Autoimmune, Experimental, Humans, Hyaluronic Acid, Multiple Sclerosis, Oligodendroglia, Stem Cells, Hyaluronan Receptors, Mice

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