Multiple sclerosis: re-expression of a developmental pathway that restricts oligodendrocyte maturation - PubMed (original) (raw)
. 2002 Oct;8(10):1115-21.
doi: 10.1038/nm781. Epub 2002 Sep 23.
Affiliations
- PMID: 12357247
- DOI: 10.1038/nm781
Multiple sclerosis: re-expression of a developmental pathway that restricts oligodendrocyte maturation
Gareth R John et al. Nat Med. 2002 Oct.
Abstract
During mammalian central nervous system (CNS) development, contact-mediated activation of Notch1 receptors on oligodendrocyte precursors by the ligand Jagged1 induces Hes5, which inhibits maturation of these cells. Here we tested whether the Notch pathway is re-expressed in the adult CNS in multiple sclerosis (MS), an inflammatory demyelinating disease in which remyelination is typically limited. We found that transforming growth factor-beta 1 (TGF-beta 1), a cytokine upregulated in MS, specifically re-induced Jagged1 in primary cultures of human astrocytes. Within and around active MS plaques lacking remyelination, Jagged1 was expressed at high levels by hypertrophic astrocytes, whereas Notch1 and Hes5 localized to cells with an immature oligodendrocyte phenotype, and TGF-beta 1 was associated with perivascular extracellular matrix in the same areas. In contrast, there was negligible Jagged1 expression in remyelinated lesions. Experiments in vitro showed that Jagged1 signaling inhibited process outgrowth from primary human oligodendrocytes. These data are the first to implicate the Notch pathway in the limited remyelination in MS. Thus, Notch may represent a potential target for therapeutic intervention in this disease.
Comment in
- Myelin failure in multiple sclerosis: breaking the spell of Notch.
Hohlfeld R. Hohlfeld R. Nat Med. 2002 Oct;8(10):1075-6. doi: 10.1038/nm1002-1075. Nat Med. 2002. PMID: 12357237 No abstract available.
Similar articles
- Notch1 and Jagged1 are expressed after CNS demyelination, but are not a major rate-determining factor during remyelination.
Stidworthy MF, Genoud S, Li WW, Leone DP, Mantei N, Suter U, Franklin RJ. Stidworthy MF, et al. Brain. 2004 Sep;127(Pt 9):1928-41. doi: 10.1093/brain/awh217. Epub 2004 Aug 2. Brain. 2004. PMID: 15289265 - Notch1 and its ligand Jagged1 are present in remyelination in a T-cell- and antibody-mediated model of inflammatory demyelination.
Seifert T, Bauer J, Weissert R, Fazekas F, Storch MK. Seifert T, et al. Acta Neuropathol. 2007 Feb;113(2):195-203. doi: 10.1007/s00401-006-0170-9. Epub 2006 Nov 30. Acta Neuropathol. 2007. PMID: 17136549 - TGFbeta1 induces Jagged1 expression in astrocytes via ALK5 and Smad3 and regulates the balance between oligodendrocyte progenitor proliferation and differentiation.
Zhang Y, Zhang J, Navrazhina K, Argaw AT, Zameer A, Gurfein BT, Brosnan CF, John GR. Zhang Y, et al. Glia. 2010 Jun;58(8):964-74. doi: 10.1002/glia.20978. Glia. 2010. PMID: 20169621 Free PMC article. - Notch signalling pathway and human diseases.
Joutel A, Tournier-Lasserve E. Joutel A, et al. Semin Cell Dev Biol. 1998 Dec;9(6):619-25. doi: 10.1006/scdb.1998.0261. Semin Cell Dev Biol. 1998. PMID: 10075489 Review. - Axoglial interaction via the notch receptor in oligodendrocyte differentiation.
Hu QD, Cui XY, Ng YK, Xiao ZC. Hu QD, et al. Ann Acad Med Singap. 2004 Sep;33(5):581-8. Ann Acad Med Singap. 2004. PMID: 15531953 Review.
Cited by
- Deciphering Oligodendrocyte Lineages in the Human Fetal Central Nervous System Using Single-Cell RNA Sequencing.
Zheng C, Tu C, Wang J, Yu Y, Guo X, Sun J, Sun J, Cai W, Yang Q, Sun T. Zheng C, et al. Mol Neurobiol. 2024 Mar;61(3):1737-1752. doi: 10.1007/s12035-023-03661-9. Epub 2023 Sep 29. Mol Neurobiol. 2024. PMID: 37775719 - Genetic Inactivation of Notch1 Synergizes with Loss of Trp53 to Induce Tumor Formation in the Adult Mouse Forebrain.
Parmigiani E, Giachino C. Parmigiani E, et al. Cancers (Basel). 2022 Nov 2;14(21):5409. doi: 10.3390/cancers14215409. Cancers (Basel). 2022. PMID: 36358826 Free PMC article. - CAQK, a peptide associating with extracellular matrix components targets sites of demyelinating injuries.
Abi-Ghanem C, Jonnalagadda D, Chun J, Kihara Y, Ranscht B. Abi-Ghanem C, et al. Front Cell Neurosci. 2022 Aug 22;16:908401. doi: 10.3389/fncel.2022.908401. eCollection 2022. Front Cell Neurosci. 2022. PMID: 36072569 Free PMC article. - Multiple Sclerosis and Aging: The Dynamics of Demyelination and Remyelination.
Correale J, Ysrraelit MC. Correale J, et al. ASN Neuro. 2022 Jan-Dec;14:17590914221118502. doi: 10.1177/17590914221118502. ASN Neuro. 2022. PMID: 35938615 Free PMC article. Review. - Bu Shen Yi Sui Capsules Promote Remyelination by Regulating MicroRNA-219 and MicroRNA-338 in Exosomes to Promote Oligodendrocyte Precursor Cell Differentiation.
Ji J, Sun YQ, Zha Z, Xue B, Li JL, Jin LY, Qi F, Zhang N, Zhao H, Fan YP, Wang L. Ji J, et al. Evid Based Complement Alternat Med. 2022 Apr 13;2022:3341481. doi: 10.1155/2022/3341481. eCollection 2022. Evid Based Complement Alternat Med. 2022. PMID: 35463062 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
- MH55477/MH/NIMH NIH HHS/United States
- NS08952/NS/NINDS NIH HHS/United States
- NS11920/NS/NINDS NIH HHS/United States
- NS38102/NS/NINDS NIH HHS/United States
- NS40137/NS/NINDS NIH HHS/United States
- RG3020/RG/CSR NIH HHS/United States
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Miscellaneous