Adaptor protein MyD88 confers the susceptibility to stress via amplifying immune danger signals.
Adaptor protein MyD88 confers the susceptibility to stress via amplifying immune danger signals.
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适配器蛋白MyD88通过放大免疫危险信号来赋予压力的敏感性。
DOI：
10.1016/j.bbi.2022.12.007
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发表时间：
2023-03
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
越来越多的证据支持神经炎症在精神疾病中的致病作用，包括重度抑郁症（MDD）和2019冠状病毒病（COVID-19）的神经精神症状；然而，确切的机制和治疗策略尚不清楚。在这里，我们报告髓样分化因子88 （MyD88）是一个关键的适配器，通过招募称为“myddosome”的信号复合物将toll样受体与其下游信号连接起来，在暴露于慢性社会失败压力（CSDS）或严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）刺突蛋白后，在内侧前额叶皮层（mPFC）中上调。MyD88在mPFC中的诱导表达通过放大免疫危险信号（如高迁移率组盒1和SARS-CoV-2刺突蛋白）引发神经炎症并赋予应激易感性。MyD88过表达加重，而敲除或药物抑制MyD88可改善csds诱导的抑郁样行为。值得注意的是，新合成的MyD88二聚化靶向抑制剂TJ-M2010-5可减轻CSDS-和SARS-CoV-2刺突蛋白诱导的抑郁样行为。综上所述，我们的研究结果表明，抑制MyD88信号传导是治疗压力相关精神障碍（如重度抑郁症和covid -19相关神经精神症状）的一种有希望的治疗策略。
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.
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肺炎，降低氧饱和百分比和免疫激活之间的相互作用介导了抑郁症，焦虑和慢性疲劳综合征，因为COVID-19引起的类似于-19的症状：一种名义上的网络方法。
影响因子：
6.6
作者：
Al-Jassas HK;Al-Hakeim HK;Maes M
通讯作者：
Maes M
影响因子：
8.2
作者：
Costanza A;Amerio A;Aguglia A;Serafini G;Amore M;Hasler R;Ambrosetti J;Bondolfi G;Sampogna G;Berardelli I;Fiorillo A;Pompili M;Nguyen KD
通讯作者：
Nguyen KD
影响因子：
16.6
作者：
Dion-Albert L;Cadoret A;Doney E;Kaufmann FN;Dudek KA;Daigle B;Parise LF;Cathomas F;Samba N;Hudson N;Lebel M;Signature Consortium;Campbell M;Turecki G;Mechawar N;Menard C
通讯作者：
Menard C
DOI：
10.1016/j.bbi.2021.12.007
发表时间：
2022-03
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Frank MG;Nguyen KH;Ball JB;Hopkins S;Kelley T;Baratta MV;Fleshner M;Maier SF
通讯作者：
Maier SF
影响因子：
5.6
作者：
Ding, Zuochuan;Du, Dunfeng;Zhou, Ping
通讯作者：
Zhou, Ping