New genetic clues on multiple sclerosis risk
Date:
January 28, 2022
Source:
Karolinska Institutet
Summary:
An international team of researchers has discovered that a cell
type in the central nervous system known as oligodendrocytes might
have a different role in the development of multiple sclerosis
(MS) than previously thought. The findings could open for new
therapeutical approaches to MS.
FULL STORY ==========================================================================
An international team of researchers led by Karolinska Institutet in
Sweden have discovered that a cell type in the central nervous system
known as oligodendrocytes might have a different role in the development
of multiple sclerosis (MS) than previously thought. The findings,
published in the journal Neuron, could open for new therapeutical
approaches to MS.
==========================================================================
MS is driven by immune cells attacking oligodendrocytes and the myelin
they produce, which is an insulating layer ensheathing nerve cells. These attacks disrupt information flow in the brain and spinal cord and causes
nerve damage that triggers symptoms associated with MS such as tremors
and loss of gait.
Understanding which mechanisms influence the risk of MS is central
to finding effective therapies. Previous genetic studies have found
regions in the human genome that contain mutations (single nucleotide polymorphisms) associated with increased risk of MS.Many of these regions
are localized near genes that are active in immune cells.
Open configuration of the genome In this study, the researchers show in
mice and human brain samples that oligodendrocytes and their progenitors
have an open configuration of the genome near immune genes and at
MS-risk associated regions. This suggests that the MS risk mutations
may have a role in the activation of nearby genes in oligodendrocytes
and their progenitors, meaning they could play a more important part
than previously thought in the development of MS.
"Our findings suggest that the risk for multiple sclerosis might manifest
by misfunction not only of immune cells, but also of oligodendrocytes
and their precursor cells," says Gonc,alo Castelo-Branco, professor
at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, who conducted the study with co-first authors Mandy Meijer,
a PhD student, and Eneritz Agirre, a researcher. "These findings indicate
that these cells can also be targeted for therapeutical approaches for
MS, to prevent misfunction that might be caused by these mutations."
The study was funded by the European Union Horizon 2020, European
Committee for Treatment and Research in Multiple Sclerosis, Swedish
Research Council, the Swedish Brain Foundation, the Swedish Cancer
Society, Knut and Alice Wallenberg Foundation, the Swedish Society
for Medical Research, the Ming Wai Lau Centre for Reparative Medicine,
"La Caixa" Foundation, NIH, the National Institute on Aging, the Olav
Thon Foundation and Karolinska Institutet.
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may be edited for style and length.
========================================================================== Journal Reference:
1. Mandy Meijer, Eneritz Agirre, Mukund Kabbe, Cassandra A. van
Tuijn, Abeer
Heskol, Chao Zheng, Ana Mendanha Falca~o, Marek Bartosovic,
Leslie Kirby, Daniela Calini, Michael R. Johnson, M. Ryan
Corces, Thomas J. Montine, Xingqi Chen, Howard Y. Chang, Dheeraj
Malhotra, and Gonc,alo Castelo- Branco. Epigenomic priming of
immune genes implicates oligodendroglia in multiple sclerosis
susceptibility. Neuron, 2022 DOI: 10.1016/ j.neuron.2021.12.034 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/01/220128141316.htm
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