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http://hdl.handle.net/1942/41836
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DC Field | Value | Language |
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dc.contributor.author | SPAAS, Jan | - |
dc.contributor.author | Van der Stede, Thibaux | - |
dc.contributor.author | de Jager, Sarah | - |
dc.contributor.author | VAN DE WATERWEG BERENDS, Annet | - |
dc.contributor.author | TIANE, Assia | - |
dc.contributor.author | Baelde, Hans | - |
dc.contributor.author | Baba, Shahid P. | - |
dc.contributor.author | Eckhardt, Matthias | - |
dc.contributor.author | WOLFS, Esther | - |
dc.contributor.author | VANMIERLO, Tim | - |
dc.contributor.author | HELLINGS, Niels | - |
dc.contributor.author | OP 'T EIJNDE, Bert | - |
dc.contributor.author | Derave, Wim | - |
dc.date.accessioned | 2023-11-17T08:02:30Z | - |
dc.date.available | 2023-11-17T08:02:30Z | - |
dc.date.issued | 2023 | - |
dc.date.submitted | 2023-11-17T07:51:04Z | - |
dc.identifier.citation | PROGRESS IN NEUROBIOLOGY, 231 (Art N° 102532) | - |
dc.identifier.uri | http://hdl.handle.net/1942/41836 | - |
dc.description.abstract | Multiple sclerosis (MS) pathology features autoimmune-driven neuroinflammation, demyelination, and failed remyelination. Carnosine is a histidine-containing dipeptide (HCD) with pluripotent homeostatic properties that is able to improve outcomes in an animal MS model (EAE) when supplied exogenously. To uncover if endogenous carnosine is involved in, and protects against, MS-related neuroinflammation, demyelination or remyelination failure, we here studied the HCD-synthesizing enzyme carnosine synthase (CARNS1) in human MS lesions and two preclinical mouse MS models (EAE, cuprizone). We demonstrate that due to its presence in oligodendrocytes, CARNS1 expression is diminished in demyelinated MS lesions and mouse models mimicking demyelination/ inflammation, but returns upon remyelination. Carns1-KO mice that are devoid of endogenous HCDs display exaggerated neuroinflammation and clinical symptoms during EAE, which could be partially rescued by exogenous carnosine treatment. Worsening of the disease appears to be driven by a central, not peripheral immunemodulatory, mechanism possibly linked to impaired clearance of the reactive carbonyl acrolein in Carns1-KO mice. In contrast, CARNS1 is not required for normal oligodendrocyte precursor cell differentiation and (re) myelin to occur, and neither endogenous nor exogenous HCDs protect against cuprizone-induced demyelination. In conclusion, the loss of CARNS1 from demyelinated MS lesions can aggravate disease progression through weakening the endogenous protection against neuroinflammation. | - |
dc.description.sponsorship | This work was supported by the Special Research Fund (BOF R-8156, Hasselt University, Belgium,) and Research Foundation - Flanders (1138520 N, FWO Vlaanderen, Belgium). All human brain material has been collected from donors for or from whom a written informed consent for a brain autopsy and the use of the material and clinical information for research purposes had been obtained by The Netherlands Brain Bank (NBB, Netherlands Institute for Neuroscience, Amsterdam; open access www. brainbank.nl). The experiment protocols and methods used for analysing brain samples were conducted with the approval of the NBB and the Medical Ethical Committee of Hasselt University, and carried out according to institutional guidelines. The technical assistance of Anneke Volkaert (Ghent University) and the support from the University Biobank Limburg (UbiLim, prof. Veerle Somers) are greatly appreciated. We thank Flamma (Flamma Group, Chignolo d′Isola, Italy) for providing L-Carnosine. Supplementary Fig S4a, S8a and S9a were created in BioRender. | - |
dc.language.iso | en | - |
dc.publisher | PERGAMON-ELSEVIER SCIENCE LTD | - |
dc.rights | 2023 Elsevier Ltd. All rights reserved. | - |
dc.subject.other | Multiple sclerosis | - |
dc.subject.other | Experimental autoimmune encephalomyelitis | - |
dc.subject.other | Cuprizone | - |
dc.subject.other | CARNS1 | - |
dc.subject.other | Histidine-containing dipeptides | - |
dc.subject.other | Carnosine | - |
dc.title | Carnosine synthase deficiency aggravates neuroinflammation in multiple sclerosis | - |
dc.type | Journal Contribution | - |
dc.identifier.volume | 231 | - |
local.format.pages | 14 | - |
local.bibliographicCitation.jcat | A1 | - |
dc.description.notes | Derave, W (corresponding author), Watersportlaan 2, B-9000 Ghent, Belgium. | - |
dc.description.notes | wim.derave@ugent.be | - |
local.publisher.place | THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND | - |
local.type.refereed | Refereed | - |
local.type.specified | Article | - |
local.bibliographicCitation.artnr | 102532 | - |
dc.identifier.doi | 10.1016/j.pneurobio.2023.102532 | - |
dc.identifier.pmid | 37774767 | - |
dc.identifier.isi | 001088827200001 | - |
dc.contributor.orcid | SPAAS, Jan/0000-0002-4953-2505; van de Waterweg Berends, | - |
dc.contributor.orcid | Annet/0000-0003-2992-439X | - |
local.provider.type | wosris | - |
local.description.affiliation | [Spaas, Jan; Berends, Annet van de Waterweg; Tiane, Assia; Vanmierlo, Tim; Hellings, Niels; Eijnde, Bert O.] Univ MS Ctr UMSC, Hasselt Pelt, Belgium. | - |
local.description.affiliation | [Spaas, Jan; Berends, Annet van de Waterweg; Wolfs, Esther; Vanmierlo, Tim; Hellings, Niels; Eijnde, Bert O.] Hasselt Univ, BIOMED Biomed Res Inst, Fac Med & Life Sci, Diepenbeek, Belgium. | - |
local.description.affiliation | [Spaas, Jan; Van der Stede, Thibaux; de Jager, Sarah; Derave, Wim] Univ Ghent, Fac Med & Hlth Sci, Dept Movement & Sports Sci, Ghent, Belgium. | - |
local.description.affiliation | [Van der Stede, Thibaux] Univ Copenhagen, Dept Nutr Exercise & Sports, Copenhagen, Denmark. | - |
local.description.affiliation | [Berends, Annet van de Waterweg] ULiege, FARAH, Fac Vet Med, Lab Immunol & Vaccinol, Liege, Belgium. | - |
local.description.affiliation | [Tiane, Assia; Vanmierlo, Tim] Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Div Translat Neurosci, Maastricht, Netherlands. | - |
local.description.affiliation | [Baelde, Hans] Leiden Univ Med Ctr, Dept Pathol, Leiden, Netherlands. | - |
local.description.affiliation | [Baba, Shahid P.] Univ Louisville, Diabet & Obes Ctr, Louisville, KY USA. | - |
local.description.affiliation | [Eckhardt, Matthias] Univ Bonn, Inst Biochem & Mol Biol, Med Fac, Bonn, Germany. | - |
local.description.affiliation | [Derave, Wim] Watersportlaan 2, B-9000 Ghent, Belgium. | - |
local.uhasselt.international | yes | - |
item.fullcitation | SPAAS, Jan; Van der Stede, Thibaux; de Jager, Sarah; VAN DE WATERWEG BERENDS, Annet; TIANE, Assia; Baelde, Hans; Baba, Shahid P.; Eckhardt, Matthias; WOLFS, Esther; VANMIERLO, Tim; HELLINGS, Niels; OP 'T EIJNDE, Bert & Derave, Wim (2023) Carnosine synthase deficiency aggravates neuroinflammation in multiple sclerosis. In: PROGRESS IN NEUROBIOLOGY, 231 (Art N° 102532). | - |
item.contributor | SPAAS, Jan | - |
item.contributor | Van der Stede, Thibaux | - |
item.contributor | de Jager, Sarah | - |
item.contributor | VAN DE WATERWEG BERENDS, Annet | - |
item.contributor | TIANE, Assia | - |
item.contributor | Baelde, Hans | - |
item.contributor | Baba, Shahid P. | - |
item.contributor | Eckhardt, Matthias | - |
item.contributor | WOLFS, Esther | - |
item.contributor | VANMIERLO, Tim | - |
item.contributor | HELLINGS, Niels | - |
item.contributor | OP 'T EIJNDE, Bert | - |
item.contributor | Derave, Wim | - |
item.accessRights | Open Access | - |
item.fulltext | With Fulltext | - |
crisitem.journal.issn | 0301-0082 | - |
crisitem.journal.eissn | 1873-5118 | - |
Appears in Collections: | Research publications |
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Carnosine synthase deficiency aggravates neuroinflammation in multiple sclerosis.pdf Restricted Access | Published version | 13.26 MB | Adobe PDF | View/Open Request a copy |
Carnosine synthase deficiency aggravates neuroinflammation in multiple sclerosis.pdf | Non Peer-reviewed author version | 34.3 MB | Adobe PDF | View/Open |
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