Asset Details
Do you wish to reserve the book?
Multiple sclerosis: Re-expression of a developmental pathway that restricts oligodendrocyte maturation
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Multiple sclerosis: Re-expression of a developmental pathway that restricts oligodendrocyte maturation
Do you wish to request the book?
Multiple sclerosis: Re-expression of a developmental pathway that restricts oligodendrocyte maturation
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Multiple sclerosis: Re-expression of a developmental pathway that restricts oligodendrocyte maturation
2002
Overview
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-β1 (TGF-β1), 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-β1 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.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Biomedical and Life Sciences
/ Humans
/ Intercellular Signaling Peptides and Proteins
/ Lesions
/ Ligands
/ Mammals
/ Membrane Proteins - metabolism
/ Multiple Sclerosis - pathology
/ Multiple Sclerosis - physiopathology
/ Oligodendroglia - physiology
/ Oligonucleotide Array Sequence Analysis
/ Proteins
/ Receptors, Cell Surface - metabolism
/ Signal Transduction - physiology
