Adaptor protein MyD88 confers the susceptibility to stress via amplifying immune danger signals.
Coronavirus disease 2019
Depression
MyD88
Proinflammatory
Stress
Journal
Brain, behavior, and immunity
ISSN: 1090-2139
Titre abrégé: Brain Behav Immun
Pays: Netherlands
ID NLM: 8800478
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
received:
27
05
2022
revised:
27
11
2022
accepted:
04
12
2022
pubmed:
11
12
2022
medline:
25
1
2023
entrez:
10
12
2022
Statut:
ppublish
Résumé
Increasing evidence supports the pathogenic role of neuroinflammation in psychiatric diseases, including major depressive disorder (MDD) and neuropsychiatric symptoms of Coronavirus disease 2019 (COVID-19); however, the precise mechanism and therapeutic strategy are poorly understood. Here, we report that myeloid differentiation factor 88 (MyD88), a pivotal adaptor that bridges toll-like receptors to their downstream signaling by recruiting the signaling complex called 'myddosome', was up-regulated in the medial prefrontal cortex (mPFC) after exposure to chronic social defeat stress (CSDS) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. The inducible expression of MyD88 in the mPFC primed neuroinflammation and conferred stress susceptibility via amplifying immune danger signals, such as high-mobility group box 1 and SARS-CoV-2 spike protein. Overexpression of MyD88 aggravated, whereas knockout or pharmacological inhibition of MyD88 ameliorated CSDS-induced depressive-like behavior. Notably, TJ-M2010-5, a novel synthesized targeting inhibitor of MyD88 dimerization, alleviated both CSDS- and SARS-CoV-2 spike protein-induced depressive-like behavior. Taken together, our findings indicate that inhibiting MyD88 signaling represents a promising therapeutic strategy for stress-related mental disorders, such as MDD and COVID-19-related neuropsychiatric symptoms.
Identifiants
pubmed: 36496170
pii: S0889-1591(22)00465-2
doi: 10.1016/j.bbi.2022.12.007
pmc: PMC9726649
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Myeloid Differentiation Factor 88
0
spike protein, SARS-CoV-2
0
MYD88 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
204-220Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Références
Mol Psychiatry. 2018 Mar;23(3):556-568
pubmed: 28416811
Nature. 2010 Jun 17;465(7300):885-90
pubmed: 20485341
Brain Behav Immun. 2022 Feb;100:267-277
pubmed: 34915155
Biol Psychiatry. 2019 Feb 1;85(3):202-213
pubmed: 30454851
Mol Psychiatry. 2021 Apr;26(4):1044-1059
pubmed: 33328588
J Biol Chem. 2011 Jul 29;286(30):26470-9
pubmed: 21665946
Nat Immunol. 2021 Jul;22(7):829-838
pubmed: 33963333
Nat Commun. 2022 Jan 10;13(1):164
pubmed: 35013188
Trends Immunol. 2011 Mar;32(3):104-9
pubmed: 21269878
J Dent Res. 2011 Apr;90(4):417-27
pubmed: 20940366
Front Cell Neurosci. 2021 Feb 18;15:647378
pubmed: 33737867
Brain Behav Immun. 2018 May;70:257-267
pubmed: 29524458
Viruses. 2021 Jan 19;13(1):
pubmed: 33477869
Brain Behav Immun. 2016 Mar;53:207-222
pubmed: 26772151
Biol Psychiatry. 2021 Mar 15;89(6):615-626
pubmed: 33190845
Br J Pharmacol. 2013 Nov;170(5):1078-91
pubmed: 23941302
Pharmacol Res. 2020 Jul;157:104769
pubmed: 32275963
Nat Rev Immunol. 2020 Feb;20(2):95-112
pubmed: 31558839
Trends Neurosci. 2022 May;45(5):358-368
pubmed: 35279295
Mol Psychiatry. 2010 Apr;15(4):404-14
pubmed: 19773812
Brain Behav Immun. 2009 Oct;23(7):936-44
pubmed: 19416750
Brain Behav Immun. 2015 Aug;48:1-7
pubmed: 25816800
Cell. 2020 Mar 19;180(6):1044-1066
pubmed: 32164908
Cell Res. 2021 Jul;31(7):818-820
pubmed: 33742149
Biol Psychiatry. 2014 Oct 1;76(7):575-84
pubmed: 24289885
J Exp Med. 2021 Mar 1;218(3):
pubmed: 33433624
Mediators Inflamm. 2021 Jan 14;2021:8874339
pubmed: 33505220
Lancet. 2021 Jan 16;397(10270):220-232
pubmed: 33428867
Hepatol Res. 2019 Oct;49(10):1182-1194
pubmed: 31074165
Front Aging Neurosci. 2021 Jan 14;12:620946
pubmed: 33519423
Int Immunopharmacol. 2019 Feb;67:356-365
pubmed: 30583234
J Nutr Biochem. 2017 Jan;39:134-144
pubmed: 27833054
J Cell Biol. 2021 Jul 5;220(7):
pubmed: 33956941
Oncoimmunology. 2012 Oct 1;1(7):1165-1166
pubmed: 23170266
J Mol Neurosci. 2022 Jun;72(6):1166-1181
pubmed: 35322375
J Neurosci. 2016 Jul 27;36(30):7946-56
pubmed: 27466339
J Clin Invest. 2015 Feb;125(2):539-50
pubmed: 25562324
Neurosci Biobehav Rev. 2022 May;136:104606
pubmed: 35289272
Protein Cell. 2013 Jan;4(1):27-39
pubmed: 22996173
Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2669-74
pubmed: 20133768
J Clin Invest. 2012 Apr;122(4):1377-92
pubmed: 22406537
Biol Psychiatry. 2019 Jul 15;86(2):131-142
pubmed: 31076080
Neurobiol Stress. 2021 Sep 04;15:100390
pubmed: 34527794
Elife. 2021 Dec 06;10:
pubmed: 34866574
Lancet Neurol. 2020 Nov;19(11):919-929
pubmed: 33031735
Front Neurosci. 2021 Mar 12;15:621446
pubmed: 33790733
Biol Psychiatry. 2018 Jan 1;83(1):50-60
pubmed: 28882317
Int J Psychiatry Clin Pract. 2014 Jan;18(1):41-4
pubmed: 24168294
Biol Psychiatry. 2020 Sep 1;88(5):415-425
pubmed: 32220499
Nat Neurosci. 2017 Dec;20(12):1752-1760
pubmed: 29184215
Nat Rev Neurosci. 2008 Jan;9(1):46-56
pubmed: 18073775
J Neuroinflammation. 2019 Jan 16;16(1):10
pubmed: 30651105
Neuron. 2018 Nov 7;100(3):551-563.e7
pubmed: 30220511
J Natl Cancer Inst. 2015 Dec 28;108(4):
pubmed: 26712311
J Affect Disord. 2022 Jan 15;297:233-245
pubmed: 34699853
Cold Spring Harb Perspect Biol. 2009 Dec;1(6):a001651
pubmed: 20457564
Lancet. 2021 Aug 28;398(10302):747-758
pubmed: 34454673
Neuron. 2021 Aug 18;109(16):2573-2589.e9
pubmed: 34233151
Signal Transduct Target Ther. 2021 Sep 6;6(1):337
pubmed: 34489403
Nat Neurosci. 2021 Mar;24(3):368-378
pubmed: 33328624
Mol Neurobiol. 2022 Jan;59(1):445-458
pubmed: 34709564
JAMA Psychiatry. 2021 Jan 1;78(1):9-10
pubmed: 32579160
Cell Death Differ. 2017 Nov;24(11):1975-1986
pubmed: 28885616
Int Immunopharmacol. 2020 Aug;85:106648
pubmed: 32504998
Brain. 2022 Dec 19;145(12):4193-4201
pubmed: 36004663
Heliyon. 2021 Feb 02;7(2):e06187
pubmed: 33644468
Pharmacol Res. 2021 Jan;163:105355
pubmed: 33285230
Oncol Rep. 2019 Nov;42(5):1755-1766
pubmed: 31432184
Neuropharmacology. 2019 Mar 1;146:149-153
pubmed: 30496753
Transplantation. 2017 Feb;101(2):284-293
pubmed: 27607533