Fatty acid elongation by ELOVL6 hampers remyelination by promoting inflammatory foam cell formation during demyelination.
fatty acid metabolism
macrophage
multiple sclerosis
remyelination
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
12 09 2023
12 09 2023
Historique:
pmc-release:
05
03
2024
medline:
7
9
2023
pubmed:
5
9
2023
entrez:
5
9
2023
Statut:
ppublish
Résumé
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 monounsaturated C16 fatty acids into C18 species, was found to be up-regulated in myelin phagocytosing phagocytes in vitro and in MS lesions. Depletion of
Identifiants
pubmed: 37669365
doi: 10.1073/pnas.2301030120
pmc: PMC10500284
doi:
Substances chimiques
Fatty Acids
0
Fatty Acids, Monounsaturated
0
Elovl6 protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2301030120Références
J Biol Chem. 2005 Nov 4;280(44):37118-29
pubmed: 16118219
Arterioscler Thromb Vasc Biol. 2011 Sep;31(9):1973-9
pubmed: 21817094
Nutr Hosp. 2012 Jul-Aug;27(4):978-90
pubmed: 23165533
J Neuroimmunol. 2005 Apr;161(1-2):113-22
pubmed: 15748950
Nature. 2021 Apr;592(7853):290-295
pubmed: 33658712
Acta Neuropathol. 2014 Aug;128(2):191-213
pubmed: 24952885
Prog Lipid Res. 2010 Apr;49(2):186-99
pubmed: 20018209
Front Cell Dev Biol. 2016 May 20;4:47
pubmed: 27243011
Cell Signal. 2014 Oct;26(10):2249-58
pubmed: 25035231
Int J Mol Sci. 2021 Jul 29;22(15):
pubmed: 34360931
Lancet Neurol. 2010 May;9(5):520-32
pubmed: 20398859
Biomedicines. 2019 Feb 20;7(1):
pubmed: 30791637
Drugs R D. 2020 Sep;20(3):197-207
pubmed: 32696271
J Biol Chem. 2015 Jul 3;290(27):16979-88
pubmed: 25987561
J Neuroinflammation. 2013 Mar 04;10:35
pubmed: 23452918
Annu Rev Immunol. 2020 Apr 26;38:759-784
pubmed: 32340572
Mt Sinai J Med. 2011 Mar-Apr;78(2):244-57
pubmed: 21425268
Adv Drug Deliv Rev. 2020;159:198-213
pubmed: 31987838
BMC Neurol. 2015 Aug 27;15:154
pubmed: 26311235
Future Neurol. 2007 Nov;2(6):689-697
pubmed: 19079759
Arterioscler Thromb Vasc Biol. 2008 Jun;28(6):1050-9
pubmed: 18323516
Nat Med. 2007 Oct;13(10):1193-202
pubmed: 17906635
Nat Rev Immunol. 2011 Jun;11(6):403-15
pubmed: 21546914
Arterioscler Thromb Vasc Biol. 2004 Feb;24(2):230-9
pubmed: 14592855
J Lipid Res. 2019 Mar;60(3):506-515
pubmed: 30655318
Front Physiol. 2021 Jul 01;12:668330
pubmed: 34276398
PLoS One. 2012;7(9):e44998
pubmed: 22984598
Front Immunol. 2019 Jul 19;10:1706
pubmed: 31379883
Methods Mol Biol. 2009;579:375-89
pubmed: 19763486
Brain Pathol. 2001 Jan;11(1):107-16
pubmed: 11145196
Nat Neurosci. 2013 Sep;16(9):1211-1218
pubmed: 23872599
CNS Drugs. 2020 Nov;34(11):1191-1200
pubmed: 33108633
J Neuropathol Exp Neurol. 2007 Nov;66(11):975-88
pubmed: 17984680
FASEB J. 2015 Sep;29(9):3638-53
pubmed: 25985799
Int J Mol Sci. 2020 Dec 07;21(23):
pubmed: 33297574
J Neuropathol Exp Neurol. 2021 Oct 26;80(10):975-996
pubmed: 34553215
Nat Neurosci. 2020 Feb;23(2):194-208
pubmed: 31959936
Cell Stem Cell. 2012 Jan 6;10(1):96-103
pubmed: 22226359
Hepatology. 2020 May;71(5):1609-1625
pubmed: 31529722
J Neurochem. 2001 Nov;79(3):606-16
pubmed: 11701764
Nat Rev Neurosci. 2008 Nov;9(11):839-55
pubmed: 18931697
Science. 2018 Feb 9;359(6376):684-688
pubmed: 29301957
J Neuroinflammation. 2022 Jun 17;19(1):157
pubmed: 35715809
Cell Metab. 2023 May 2;35(5):855-874.e5
pubmed: 37084732
Oncotarget. 2017 May 30;8(22):36898-36929
pubmed: 28415564
Clin Exp Pharmacol Physiol. 2017 May;44(5):566-575
pubmed: 28135761
Trends Immunol. 2003 Jul;24(7):358-63
pubmed: 12860525
Brain. 2006 Feb;129(Pt 2):517-26
pubmed: 16364958
Annu Rev Cell Dev Biol. 2006;22:129-57
pubmed: 16753029
J Exp Med. 2020 May 4;217(5):
pubmed: 32097464
Neurobiol Dis. 2005 Feb;18(1):166-75
pubmed: 15649707
Gigascience. 2019 Jun 1;8(6):
pubmed: 31141612
Front Cell Dev Biol. 2019 Oct 01;7:210
pubmed: 31632963
Acta Neuropathol Commun. 2013 Aug 02;1:43
pubmed: 24252308
Prog Lipid Res. 2012 Jul;51(3):267-71
pubmed: 22266797