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http://hdl.handle.net/1942/42213
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DC Field | Value | Language |
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dc.contributor.author | GARCIA CORRALES, Aida | - |
dc.contributor.author | VERBERK, Sanne | - |
dc.contributor.author | HAIDAR, Mansour | - |
dc.contributor.author | GRAJCHEN, Elien | - |
dc.contributor.author | Dehairs, Jonas | - |
dc.contributor.author | VANHERLE, Sam | - |
dc.contributor.author | LOIX, Melanie | - |
dc.contributor.author | WEYTJENS, Tine | - |
dc.contributor.author | GERVOIS, Pascal | - |
dc.contributor.author | Matsuzaka, Takashi | - |
dc.contributor.author | LAMBRICHTS, Ivo | - |
dc.contributor.author | Swinnen, Johannes V. | - |
dc.contributor.author | BOGIE, Jeroen | - |
dc.contributor.author | HENDRIKS, Jerome | - |
dc.date.accessioned | 2024-01-22T14:10:23Z | - |
dc.date.available | 2024-01-22T14:10:23Z | - |
dc.date.issued | 2023 | - |
dc.date.submitted | 2024-01-22T11:21:47Z | - |
dc.identifier.citation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 120 (37) (Art N° e2301030120) | - |
dc.identifier.uri | http://hdl.handle.net/1942/42213 | - |
dc.description.abstract | A hallmark of multiple sclerosis (MS) is the formation of multiple focal demyelinating lesions within the central nervous system (CNS). These lesions mainly consist of phagocytes that play a key role in lesion progression and remyelination, and therefore represent a promising therapeutic target in MS. We recently showed that unsaturated fatty acids produced by stearoyl-CoA desaturase-1 induce inflammatory foam cell formation during demyelination. These fatty acids are elongated by the "elongation of very long chain fatty acids" proteins (ELOVLs), generating a series of functionally distinct lipids. Here, we show that the expression and activity of ELOVLs are altered in myelin-induced foam cells. Especially ELOVL6, an enzyme responsible for converting saturated and mono-unsaturated C16 fatty acids into C18 species, was found to be up-regulated in myelin phagocytosing phagocytes in vitro and in MS lesions. Depletion of Elovl6 induced a repair-promoting phagocyte phenotype through activation of the S1P/PPAR. pathway. Elovl6-deficient foamy macrophages showed enhanced ABCA1-mediated lipid efflux, increased production of neurotrophic factors, and reduced expression of inflammatory mediators. Moreover, our data show that ELOVL6 hampers CNS repair, as Elovl6 deficiency prevented demyelination and boosted remyelination in organotypic brain slice cultures and the mouse cuprizone model. These findings indicate that targeting ELOVL6 activity may be an effective strategy to stimulate CNS repair in MS and other neurodegenerative diseases. | - |
dc.description.sponsorship | We thank M.P. Tulleners and Frank Vanderhoydonc for their excellent technical assistance. We also thank Susan Schwab and her team (Skirball Institute of Biomolecular Medicine, New York University Langone Medical Center, USA) for providing the S1PR-GFP plasmids. The work was financially supported by the Research Foundation of Flanders (FWO Vlaanderen; G099618FWO and SBO-LipoMacs-S001623N), the Interreg V-A EMR program (EURLIPIDS and EMR23), the Belgian Charcot Foundation (2019-0009), and the special research fund UHasselt (BOF). The funding agencies had no role in the design, analysis, or writing of the article. | - |
dc.language.iso | en | - |
dc.publisher | NATL ACAD SCIENCES | - |
dc.rights | 2023 the Author(s). Published by PNAS. This article is distributed under Creative Commons Attribution-NonCommercial- NoDerivatives License 4.0 (CC BY-NC- ND). | - |
dc.subject.other | multiple sclerosis | - |
dc.subject.other | fatty acid metabolism | - |
dc.subject.other | remyelination | - |
dc.subject.other | macrophage | - |
dc.title | Fatty acid elongation by ELOVL6 hampers remyelination by promoting inflammatory foam cell formation during demyelination | - |
dc.type | Journal Contribution | - |
dc.identifier.issue | 37 | - |
dc.identifier.volume | 120 | - |
local.format.pages | 11 | - |
local.bibliographicCitation.jcat | A1 | - |
dc.description.notes | Hendriks, JJA (corresponding author), Hasselt Univ, Biomed Res Inst, Dept Immunol & Infect, B-3590 Diepenbeek, Belgium. | - |
dc.description.notes | jerome.hendriks@uhasselt.be | - |
local.publisher.place | 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA | - |
local.type.refereed | Refereed | - |
local.type.specified | Article | - |
local.bibliographicCitation.artnr | e2301030120 | - |
dc.identifier.doi | 10.1073/pnas.2301030120 | - |
dc.identifier.isi | 001119304600001 | - |
dc.contributor.orcid | Bogie, Jeroen/0000-0002-0016-1926; Matsuzaka, | - |
dc.contributor.orcid | Takashi/0000-0002-5898-3463; Gervois, Pascal/0000-0002-8320-1320 | - |
local.provider.type | wosris | - |
local.description.affiliation | [Corrales, Aida V. Garcia; Verberk, Sanne G. S.; Haidar, Mansour; Grajchen, Elien; Vanherle, Sam; Loix, Melanie; Weytjens, Tine; Bogie, Jeroen F. J.; Hendriks, Jerome J. A.] Hasselt Univ, Biomed Res Inst, Dept Immunol & Infect, B-3590 Diepenbeek, Belgium. | - |
local.description.affiliation | [Dehairs, Jonas; Swinnen, Johannes V.] Univ Leuven, Leuven Canc Inst, Lab Lipid Metab & Canc, Dept Oncol, B-3000 Leuven, Belgium. | - |
local.description.affiliation | [Gervois, Pascal; Lambrichts, Ivo] Hasselt Univ, Biomed Res Inst, Dept Cardiol & Organ Syst, B-3590 Diepenbeek, Belgium. | - |
local.description.affiliation | [Matsuzaka, Takashi] Univ Tsukuba, Fac Med, Dept Internal Med, Endocrinol & Metabol, Tsukuba, Ibaraki 3058575, Japan. | - |
local.uhasselt.international | yes | - |
item.fulltext | With Fulltext | - |
item.accessRights | Open Access | - |
item.contributor | GARCIA CORRALES, Aida | - |
item.contributor | VERBERK, Sanne | - |
item.contributor | HAIDAR, Mansour | - |
item.contributor | GRAJCHEN, Elien | - |
item.contributor | Dehairs, Jonas | - |
item.contributor | VANHERLE, Sam | - |
item.contributor | LOIX, Melanie | - |
item.contributor | WEYTJENS, Tine | - |
item.contributor | GERVOIS, Pascal | - |
item.contributor | Matsuzaka, Takashi | - |
item.contributor | LAMBRICHTS, Ivo | - |
item.contributor | Swinnen, Johannes V. | - |
item.contributor | BOGIE, Jeroen | - |
item.contributor | HENDRIKS, Jerome | - |
item.fullcitation | GARCIA CORRALES, Aida; VERBERK, Sanne; HAIDAR, Mansour; GRAJCHEN, Elien; Dehairs, Jonas; VANHERLE, Sam; LOIX, Melanie; WEYTJENS, Tine; GERVOIS, Pascal; Matsuzaka, Takashi; LAMBRICHTS, Ivo; Swinnen, Johannes V.; BOGIE, Jeroen & HENDRIKS, Jerome (2023) Fatty acid elongation by ELOVL6 hampers remyelination by promoting inflammatory foam cell formation during demyelination. In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 120 (37) (Art N° e2301030120). | - |
crisitem.journal.issn | 0027-8424 | - |
crisitem.journal.eissn | 1091-6490 | - |
Appears in Collections: | Research publications |
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Fatty acid elongation by ELOVL6 hampers remyelination by promoting inflammatory foam cell formation during demyelination.pdf Restricted Access | Published version | 3.56 MB | Adobe PDF | View/Open Request a copy |
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