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Regulation of stress granule formation in human oligodendrocytes.

Authors :
Pernin F
Cui QL
Mohammadnia A
Fernandes MGF
Hall JA
Srour M
Dudley RWR
Zandee SEJ
Klement W
Prat A
Salapa HE
Levin MC
Moore GRW
Kennedy TE
Vande Velde C
Antel JP
Source :
Nature communications [Nat Commun] 2024 Feb 19; Vol. 15 (1), pp. 1524. Date of Electronic Publication: 2024 Feb 19.
Publication Year :
2024

Abstract

Oligodendrocyte (OL) injury and subsequent loss is a pathologic hallmark of multiple sclerosis (MS). Stress granules (SGs) are membrane-less organelles containing mRNAs stalled in translation and considered as participants of the cellular response to stress. Here we show SGs in OLs in active and inactive areas of MS lesions as well as in normal-appearing white matter. In cultures of primary human adult brain derived OLs, metabolic stress conditions induce transient SG formation in these cells. Combining pro-inflammatory cytokines, which alone do not induce SG formation, with metabolic stress results in persistence of SGs. Unlike sodium arsenite, metabolic stress induced SG formation is not blocked by the integrated stress response inhibitor. Glycolytic inhibition also induces persistent SGs indicating the dependence of SG formation and disassembly on the energetic glycolytic properties of human OLs. We conclude that SG persistence in OLs in MS reflects their response to a combination of metabolic stress and pro-inflammatory conditions.<br /> (© 2024. The Author(s).)

Details

Language :
English
ISSN :
2041-1723
Volume :
15
Issue :
1
Database :
MEDLINE
Journal :
Nature communications
Publication Type :
Academic Journal
Accession number :
38374028
Full Text :
https://doi.org/10.1038/s41467-024-45746-6