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© The Rockefeller University Press, 0021-9525/2002/10/15-a $5.00
The Journal of Cell Biology, Volume 159, Number 1, 15-a-15

MS as a disease of immaturity

Turning on Notch (right) inhibits oligodendrocyte maturation. John/Macmillan

Multiple sclerosis (MS) lesions are characterized by loss of myelin, the insulating coat that surrounds axons. This is despite an abundance of the myelin-supplying glial cells called oligodendrocytes around the lesion. Gareth John, Celia Brosnan, and colleagues (Albert Einstein College of Medicine, Bronx, NY) now provide evidence that an inflammatory cascade keeps those oligodendrocytes in an immature state that does not allow for myelin production.

John started out by adding together two elements present in MS lesions: various immune molecules and glial cells called astrocytes. One change stood out: the cytokine TGFß1 caused astrocytes to make Jagged1. This ligand for Notch (which is present on oligodendrocytes) was also made by reactive astrocytes in MS lesions. Addition of Jagged1 to cultured oligodendrocytes inhibited process outgrowth, which is one measure of maturation.

During development, Jagged1 keeps oligodendrocytes in an immature state so that they can migrate to cover entire axons before beginning the sedentary process of myelination. The induction of this pathway in brain lesions may be an attempt to generate a larger pool of oligodendrocyte precursors, or it may be an unfortunate carryover from development of the immune system.

Whatever the underlying logic, the Notch pathway represents a possible target for MS treatment. The initiating immune cascades are another possible target, although here the details remain sketchy. "If we understood the actual triggers to inflammation in MS," says John, "we would be halfway to a cure."

Reference:

John, G.R., et al. 2002. Nat. Med. 10.1038/nm781.

William A. Wells

wellsw{at}rockefeller.edu

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This Article Full Text (PDF, 290K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?