The transcription factor Nurr1 is upregulated in amyotrophic lateral sclerosis patients and SOD1-G93A mice.
Amyotrophic Lateral Sclerosis
/ blood
Animals
Astrocytes
/ metabolism
Brain-Derived Neurotrophic Factor
/ metabolism
Female
Gene Expression Regulation
Humans
Male
Mice
Mice, Transgenic
Middle Aged
Motor Neurons
/ metabolism
NF-kappa B
/ genetics
Nitric Oxide Synthase Type II
/ genetics
Nuclear Receptor Subfamily 4, Group A, Member 2
/ blood
Promoter Regions, Genetic
/ genetics
RNA, Messenger
/ genetics
Spinal Cord
/ metabolism
Superoxide Dismutase-1
/ genetics
Transcription Factors
/ genetics
Transcriptional Activation
/ genetics
Up-Regulation
/ genetics
ALS
Motor neuron disease
Neuroinflammation
Nurr1
SOD1-G93A mice
Journal
Disease models & mechanisms
ISSN: 1754-8411
Titre abrégé: Dis Model Mech
Pays: England
ID NLM: 101483332
Informations de publication
Date de publication:
15 05 2020
15 05 2020
Historique:
received:
25
11
2019
accepted:
13
03
2020
pubmed:
20
3
2020
medline:
11
6
2021
entrez:
20
3
2020
Statut:
epublish
Résumé
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects both lower and upper motor neurons (MNs) in the central nervous system. ALS etiology is highly multifactorial and multifarious, and an effective treatment is still lacking. Neuroinflammation is a hallmark of ALS and could be targeted to develop new therapeutic approaches. Interestingly, the transcription factor Nurr1 has been demonstrated to have an important role in the inflammatory process in several neurological disorders, such as Parkinson's disease and multiple sclerosis. In the present paper, we demonstrate for the first time that Nurr1 expression levels are upregulated in the peripheral blood of ALS patients. Moreover, we investigated Nurr1 function in the SOD1-G93A mouse model of ALS. Nurr1 was strongly upregulated in the spinal cord during the asymptomatic and early symptomatic phases of the disease, where it promoted the expression of brain-derived neurotrophic factor mRNA and the repression of NFκB pro-inflammatory targets, such as inducible nitric oxide synthase. Therefore, we hypothesize that Nurr1 is activated in an early phase of the disease as a protective endogenous anti-inflammatory mechanism, although not sufficient to reverse disease progression. On the basis of these observations, Nurr1 could represent a potential biomarker for ALS and a promising target for future therapies.
Identifiants
pubmed: 32188741
pii: dmm.043513
doi: 10.1242/dmm.043513
pmc: PMC7240304
pii:
doi:
Substances chimiques
Brain-Derived Neurotrophic Factor
0
NF-kappa B
0
Nuclear Receptor Subfamily 4, Group A, Member 2
0
RNA, Messenger
0
Transcription Factors
0
Nitric Oxide Synthase Type II
EC 1.14.13.39
Superoxide Dismutase-1
EC 1.15.1.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2020. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interestsThe authors declare no competing or financial interests.
Références
Acta Neuropathol. 2019 May;137(5):715-730
pubmed: 30465257
Cell. 2009 Apr 3;137(1):47-59
pubmed: 19345186
Arch Pharm Res. 2016 Nov;39(11):1530-1536
pubmed: 27778276
J Neurol Sci. 2001 Oct 15;191(1-2):3-9
pubmed: 11676986
Adv Exp Med Biol. 2013;961:137-45
pubmed: 23224876
Mol Cell Biol. 2013 Dec;33(24):4936-46
pubmed: 24126056
J Cell Biol. 2009 Dec 14;187(6):761-72
pubmed: 19951898
Nat Rev Neurol. 2011 Nov;7(11):616-30
pubmed: 22051914
J Biol Chem. 2012 Jun 8;287(24):19827-40
pubmed: 22514272
Arterioscler Thromb Vasc Biol. 2006 Oct;26(10):2288-94
pubmed: 16873729
Mol Pharmacol. 2015 Jun;87(6):1021-34
pubmed: 25858541
Nature. 2003 May 29;423(6939):555-60
pubmed: 12774125
Nat Commun. 2011;2:269
pubmed: 21468021
Eur J Neurol. 2012 Jun;19(6):870-5
pubmed: 22309633
Inflamm Res. 2015 Nov;64(11):841-4
pubmed: 26337347
Nat Immunol. 2013 Mar;14(3):230-7
pubmed: 23334790
J Biol Chem. 2002 Sep 20;277(38):35118-23
pubmed: 12130634
Eur J Immunol. 2016 Aug;46(8):1842-53
pubmed: 27184189
J Steroid Biochem Mol Biol. 2016 Mar;157:48-60
pubmed: 25917081
J Neuroimmunol. 2005 Feb;159(1-2):215-24
pubmed: 15652422
Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):2360-5
pubmed: 23341612
Front Immunol. 2019 Jan 08;9:3075
pubmed: 30671056
J Neurol Sci. 2008 Oct 15;273(1-2):29-33
pubmed: 18684475
Front Cell Neurosci. 2018 Jan 30;12:17
pubmed: 29440993
Antioxid Redox Signal. 2012 Nov 1;17(9):1277-330
pubmed: 22413952
J Neurosci. 2015 May 13;35(19):7332-48
pubmed: 25972164
Front Neurosci. 2018 Aug 07;12:510
pubmed: 30131665
Cell Death Dis. 2017 Dec 20;8(12):3223
pubmed: 29259166
Cell Death Differ. 2014 Jul;21(7):1142-9
pubmed: 24632945
Cell Death Dis. 2018 Feb 12;9(2):206
pubmed: 29434186
Neurology. 2004 Apr 13;62(7):1231-2
pubmed: 15079038
Nat Rev Neurosci. 2013 Apr;14(4):248-64
pubmed: 23463272
J Neuroimmune Pharmacol. 2009 Dec;4(4):389-98
pubmed: 19731042
Nat Biotechnol. 2011 Aug 10;29(9):824-8
pubmed: 21832997
Neuropathol Appl Neurobiol. 1990 Oct;16(5):401-10
pubmed: 2263315
Br J Pharmacol. 2013 Apr;168(8):1889-901
pubmed: 23215787
Nat Genet. 2003 Jan;33(1):85-9
pubmed: 12496759
Toxicol Sci. 2018 Jun 1;163(2):569-578
pubmed: 29522201
PLoS One. 2013;8(2):e55999
pubmed: 23409108
Science. 1997 Apr 11;276(5310):248-50
pubmed: 9092472
J Neurosci. 2009 Dec 16;29(50):15923-32
pubmed: 20016108
Science. 1994 Jun 17;264(5166):1772-5
pubmed: 8209258
Curr Mol Med. 2011 Apr;11(3):246-54
pubmed: 21375489
Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):4013-8
pubmed: 9520484
Proc Natl Acad Sci U S A. 2010 Jul 6;107(27):12317-22
pubmed: 20566846
Biochem Soc Trans. 2011 Apr;39(2):688-93
pubmed: 21428963
Mol Cell Biol. 1999 Nov;19(11):7549-57
pubmed: 10523643
Lancet Neurol. 2018 Jan;17(1):94-102
pubmed: 29154141
JAMA Neurol. 2017 Dec 1;74(12):1446-1454
pubmed: 28973548
J Neuroimmune Pharmacol. 2013 Sep;8(4):888-99
pubmed: 23881705
Neurobiol Dis. 2008 Sep;31(3):395-405
pubmed: 18586098
Neurobiol Dis. 2015 May;77:1-12
pubmed: 25726748
Nat Rev Neurosci. 2006 Sep;7(9):710-23
pubmed: 16924260
Neurotox Res. 2016 Oct;30(3):338-44
pubmed: 27159982
Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17913-8
pubmed: 18997009
Neurosci Lett. 2017 May 22;650:25-32
pubmed: 28385514
Expert Opin Ther Targets. 2017 Mar;21(3):291-304
pubmed: 28055275
Neurotherapeutics. 2015 Apr;12(2):364-75
pubmed: 25567201
Cytotherapy. 2014 Aug;16(8):1059-72
pubmed: 24794182
J Biol Chem. 2012 Mar 30;287(14):11351-62
pubmed: 22294685
Autophagy. 2014 Oct 1;10(10):1827-43
pubmed: 25136804
J Neurol Sci. 2017 Aug 15;379:58-63
pubmed: 28716280
J Cell Biochem. 2012 Sep;113(9):2920-36
pubmed: 22539306
Nat Neurosci. 2014 Jan;17(1):17-23
pubmed: 24369373
Curr Opin Neurol. 2018 Oct;31(5):635-639
pubmed: 30048339
PLoS One. 2014 Sep 29;9(9):e108791
pubmed: 25265488
Front Neurosci. 2017 Jan 19;11:8
pubmed: 28154524
PLoS One. 2015 Jun 01;10(6):e0128560
pubmed: 26030275
Stem Cells. 2010 Oct;28(10):1741-50
pubmed: 20734356