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The SARS-CoV-2 main protease M pro causes microvascular brain pathology by cleaving NEMO in brain endothelial cells.

التفاصيل البيبلوغرافية
العنوان: The SARS-CoV-2 main protease M pro causes microvascular brain pathology by cleaving NEMO in brain endothelial cells.
المؤلفون: Wenzel J; Institute for Experimental and Clinical Pharmacology and Toxicology, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany.; DZHK (German Research Centre for Cardiovascular Research), Hamburg-Lübeck-Kiel and Frankfurt, Germany., Lampe J; Institute for Experimental and Clinical Pharmacology and Toxicology, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany.; DZHK (German Research Centre for Cardiovascular Research), Hamburg-Lübeck-Kiel and Frankfurt, Germany., Müller-Fielitz H; Institute for Experimental and Clinical Pharmacology and Toxicology, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany., Schuster R; Institute for Experimental and Clinical Pharmacology and Toxicology, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany., Zille M; Institute for Experimental and Clinical Pharmacology and Toxicology, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany.; DZHK (German Research Centre for Cardiovascular Research), Hamburg-Lübeck-Kiel and Frankfurt, Germany., Müller K; Institute for Experimental and Clinical Pharmacology and Toxicology, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany., Krohn M; Institute for Experimental and Clinical Pharmacology and Toxicology, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany.; DZHK (German Research Centre for Cardiovascular Research), Hamburg-Lübeck-Kiel and Frankfurt, Germany., Körbelin J; Department of Oncology, Hematology & Bone Marrow Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Zhang L; Institute of Molecular Medicine, University of Lübeck, Lübeck, Germany.; German Center for Infection Research (DZIF), partner site Hamburg-Lübeck-Borstel-Riems, Lübeck, Germany., Özorhan Ü; Institute for Experimental and Clinical Pharmacology and Toxicology, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany.; DZHK (German Research Centre for Cardiovascular Research), Hamburg-Lübeck-Kiel and Frankfurt, Germany., Neve V; Institute for Experimental and Clinical Pharmacology and Toxicology, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany., Wagner JUG; DZHK (German Research Centre for Cardiovascular Research), Hamburg-Lübeck-Kiel and Frankfurt, Germany.; Institute for Cardiovascular Regeneration, Cardiopulmonary Institute (CPI), University Frankfurt, Frankfurt, Germany., Bojkova D; Institute of Medical Virology, University Frankfurt, Frankfurt, Germany., Shumliakivska M; Institute for Cardiovascular Regeneration, Cardiopulmonary Institute (CPI), University Frankfurt, Frankfurt, Germany., Jiang Y; Institute for Experimental and Clinical Pharmacology and Toxicology, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany., Fähnrich A; Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.; Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany., Ott F; Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.; Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany., Sencio V; Centre d'Infection et d'Immunité de Lille, Inserm U1019, CNRS UMR 9017, University of Lille, CHU Lille, Institut Pasteur de Lille, Lille, France., Robil C; Centre d'Infection et d'Immunité de Lille, Inserm U1019, CNRS UMR 9017, University of Lille, CHU Lille, Institut Pasteur de Lille, Lille, France., Pfefferle S; Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Sauve F; Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S 1172, DISTALZ, EGID, Lille, France., Coêlho CFF; Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S 1172, DISTALZ, EGID, Lille, France., Franz J; Institute of Neuropathology, University Medical Center, Göttingen, Germany.; Campus Institute for Dynamics of Biological Networks, University of Göttingen, Göttingen, Germany.; Max Planck Institute for Experimental Medicine, Göttingen, Germany., Spiecker F; Institute for Experimental and Clinical Pharmacology and Toxicology, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany., Lembrich B; Institute for Experimental and Clinical Pharmacology and Toxicology, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany., Binder S; Institute for Experimental and Clinical Pharmacology and Toxicology, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany., Feller N; Institute for Experimental and Clinical Pharmacology and Toxicology, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany.; DZHK (German Research Centre for Cardiovascular Research), Hamburg-Lübeck-Kiel and Frankfurt, Germany., König P; Airway Research Center North, Member of the German Center for Lung Research (DZL), Lübeck, Germany.; Institute of Anatomy, University of Lübeck, Lübeck, Germany., Busch H; Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.; Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany., Collin L; Roche Pharma Research and Early Development (pRED), Roche Innovation Center, Basel, Switzerland., Villaseñor R; Roche Pharma Research and Early Development (pRED), Roche Innovation Center, Basel, Switzerland., Jöhren O; Institute for Experimental and Clinical Pharmacology and Toxicology, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany., Altmeppen HC; Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Pasparakis M; Institute for Genetics, University of Cologne, Cologne, Germany., Dimmeler S; DZHK (German Research Centre for Cardiovascular Research), Hamburg-Lübeck-Kiel and Frankfurt, Germany.; Institute for Cardiovascular Regeneration, Cardiopulmonary Institute (CPI), University Frankfurt, Frankfurt, Germany., Cinatl J; Institute of Medical Virology, University Frankfurt, Frankfurt, Germany., Püschel K; Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Zelic M; Rare and Neurologic Diseases Research, Sanofi, Framingham, MA, USA., Ofengeim D; Rare and Neurologic Diseases Research, Sanofi, Framingham, MA, USA., Stadelmann C; Institute of Neuropathology, University Medical Center, Göttingen, Germany., Trottein F; Centre d'Infection et d'Immunité de Lille, Inserm U1019, CNRS UMR 9017, University of Lille, CHU Lille, Institut Pasteur de Lille, Lille, France., Nogueiras R; Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain., Hilgenfeld R; Institute of Molecular Medicine, University of Lübeck, Lübeck, Germany.; German Center for Infection Research (DZIF), partner site Hamburg-Lübeck-Borstel-Riems, Lübeck, Germany., Glatzel M; Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Prevot V; Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S 1172, DISTALZ, EGID, Lille, France., Schwaninger M; Institute for Experimental and Clinical Pharmacology and Toxicology, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany. markus.schwaninger@uni-luebeck.de.; DZHK (German Research Centre for Cardiovascular Research), Hamburg-Lübeck-Kiel and Frankfurt, Germany. markus.schwaninger@uni-luebeck.de.
المصدر: Nature neuroscience [Nat Neurosci] 2021 Nov; Vol. 24 (11), pp. 1522-1533. Date of Electronic Publication: 2021 Oct 21.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: United States NLM ID: 9809671 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-1726 (Electronic) Linking ISSN: 10976256 NLM ISO Abbreviation: Nat Neurosci Subsets: MEDLINE
أسماء مطبوعة: Publication: <2002->: New York, NY : Nature Publishing Group
Original Publication: New York, NY : Nature America Inc., c1998-
مواضيع طبية MeSH: Blood-Brain Barrier/*metabolism , Brain/*metabolism , Coronavirus 3C Proteases/*metabolism , Intracellular Signaling Peptides and Proteins/*metabolism , Microvessels/*metabolism , SARS-CoV-2/*metabolism, Animals ; Blood-Brain Barrier/pathology ; Brain/pathology ; Chlorocebus aethiops ; Coronavirus 3C Proteases/genetics ; Cricetinae ; Female ; Humans ; Intracellular Signaling Peptides and Proteins/genetics ; Male ; Mesocricetus ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Microvessels/pathology ; SARS-CoV-2/genetics ; Vero Cells
مستخلص: Coronavirus disease 2019 (COVID-19) can damage cerebral small vessels and cause neurological symptoms. Here we describe structural changes in cerebral small vessels of patients with COVID-19 and elucidate potential mechanisms underlying the vascular pathology. In brains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals and animal models, we found an increased number of empty basement membrane tubes, so-called string vessels representing remnants of lost capillaries. We obtained evidence that brain endothelial cells are infected and that the main protease of SARS-CoV-2 (M pro ) cleaves NEMO, the essential modulator of nuclear factor-κB. By ablating NEMO, M pro induces the death of human brain endothelial cells and the occurrence of string vessels in mice. Deletion of receptor-interacting protein kinase (RIPK) 3, a mediator of regulated cell death, blocks the vessel rarefaction and disruption of the blood-brain barrier due to NEMO ablation. Importantly, a pharmacological inhibitor of RIPK signaling prevented the M pro -induced microvascular pathology. Our data suggest RIPK as a potential therapeutic target to treat the neuropathology of COVID-19.
(© 2021. The Author(s).)
References: Helms, J. et al. Neurologic features in severe SARS-CoV-2 infection. N. Engl. J. Med. 382, 2268–2270 (2020). (PMID: 3229433910.1056/NEJMc2008597)
Paterson, R. W. et al. The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings. Brain 143, 3104–3120 (2020). (PMID: 32637987745435210.1093/brain/awaa240)
Iadecola, C., Anrather, J. & Kamel, H. Effects of COVID-19 on the nervous system. Cell 183, 16–27 (2020). (PMID: 32882182743750110.1016/j.cell.2020.08.028)
Nalbandian, A. et al. Post-acute COVID-19 syndrome. Nat. Med. 27, 601–615 (2021). (PMID: 3375393710.1038/s41591-021-01283-z8893149)
Paniz-Mondolfi, A. et al. Central nervous system involvement by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). J. Med. Virol. 92, 699–702 (2020). (PMID: 3231481010.1002/jmv.25915)
Puelles, V. G. et al. Multiorgan and renal tropism of SARS-CoV-2. N. Engl. J. Med. 383, 590–592 (2020). (PMID: 3240215510.1056/NEJMc2011400)
Andersson, M. I. et al. SARS-CoV-2 RNA detected in blood samples from patients with COVID-19 is not associated with infectious virus. Wellcome Open Res. 5, 181 (2020). (PMID: 33283055768960310.12688/wellcomeopenres.16002.2)
Cantuti-Castelvetri, L. et al. Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. Science 370, 856–860 (2020). (PMID: 33082293785739110.1126/science.abd2985)
Meinhardt, J. et al. Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nat. Neurosci. 24, 168–175 (2021). (PMID: 3325787610.1038/s41593-020-00758-5)
Song, E. et al. Neuroinvasion of SARS-CoV-2 in human and mouse brain. J. Exp. Med. 218, e20202135 (2021). (PMID: 33433624780829910.1084/jem.20202135)
Ackermann, M. et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19. N. Engl. J. Med. 383, 120–128 (2020). (PMID: 32437596741275010.1056/NEJMoa2015432)
Varga, Z. et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet 395, 1417–1418 (2020). (PMID: 32325026717272210.1016/S0140-6736(20)30937-5)
Radmanesh, A. et al. COVID-19-associated diffuse leukoencephalopathy and microhemorrhages. Radiology 297, E223–E227 (2020). (PMID: 3243731410.1148/radiol.2020202040)
Conte, G. et al. COVID-19-associated PRES-like encephalopathy with perivascular gadolinium enhancement. AJNR Am. J. Neuroradiol. 41, 2206–2208 (2020). (PMID: 3281676910.3174/ajnr.A67627963244)
Conklin, J. et al. Susceptibility-weighted imaging reveals cerebral microvascular injury in severe COVID-19. J. Neurol. Sci. 421, 117308 (2021). (PMID: 33497950783228410.1016/j.jns.2021.117308)
Jaunmuktane, Z. et al. Microvascular injury and hypoxic damage: emerging neuropathological signatures in COVID-19. Acta Neuropathol. 140, 397–400 (2020). (PMID: 32638079734075810.1007/s00401-020-02190-2)
Reichard, R. R. et al. Neuropathology of COVID-19: a spectrum of vascular and acute disseminated encephalomyelitis (ADEM)-like pathology. Acta Neuropathol. 140, 1–6 (2020). (PMID: 32449057724599410.1007/s00401-020-02166-2)
Koralnik, I. J. & Tyler, K. L. COVID-19: a global threat to the nervous system. Ann. Neurol. 88, 1–11 (2020). (PMID: 3250654910.1002/ana.25807)
Matschke, J. et al. Neuropathology of patients with COVID-19 in Germany: a postmortem case series. Lancet Neurol. 19, 919–929 (2020). (PMID: 33031735753562910.1016/S1474-4422(20)30308-2)
Zhang, L. et al. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved alpha-ketoamide inhibitors. Science 368, 409–412 (2020). (PMID: 32198291716451810.1126/science.abb3405)
Wu, J. & Chen, Z. J. Innate immune sensing and signaling of cytosolic nucleic acids. Annu Rev. Immunol. 32, 461–488 (2014). (PMID: 2465529710.1146/annurev-immunol-032713-120156)
Kondylis, V., Kumari, S., Vlantis, K. & Pasparakis, M. The interplay of IKK, NF-κB and RIPK1 signaling in the regulation of cell death, tissue homeostasis and inflammation. Immunol. Rev. 277, 113–127 (2017). (PMID: 2846253110.1111/imr.12550)
Brown, W. R. A review of string vessels or collapsed, empty basement membrane tubes. J. Alzheimers Dis. 21, 725–739 (2010). (PMID: 20634580308164110.3233/JAD-2010-100219)
Shilts, J., Crozier, T. W. M., Greenwood, E. J. D., Lehner, P. J. & Wright, G. J. No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor. Sci. Rep. 11, 413 (2021). (PMID: 33432067780146510.1038/s41598-020-80464-1)
Hamming, I. et al. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J. Pathol. 203, 631–637 (2004). (PMID: 15141377716772010.1002/path.1570)
Hoffmann, M. et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181, 271–280 (2020). (PMID: 32142651710262710.1016/j.cell.2020.02.052)
Wang, K. et al. CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells. Signal Transduct. Target Ther. 5, 283 (2020). (PMID: 33277466771489610.1038/s41392-020-00426-x)
Lake, B. B. et al. Integrative single-cell analysis of transcriptional and epigenetic states in the human adult brain. Nat. Biotechnol. 36, 70–80 (2018). (PMID: 2922746910.1038/nbt.4038)
He, L. et al. Pericyte-specific vascular expression of SARS-CoV-2 receptor ACE2—implications for microvascular inflammation and hypercoagulopathy in COVID-19. Preprint at bioRxiv https://doi.org/10.1101/2020.05.11.088500 (2020).
Kaneko, N. et al. Flow-mediated susceptibility and molecular response of cerebral endothelia to SARS-CoV-2 infection. Stroke 52, 260–270 (2021). (PMID: 3316184310.1161/STROKEAHA.120.032764)
McCracken, I. R. et al. Lack of evidence of angiotensin-converting enzyme 2 expression and replicative infection by SARS-CoV-2 in human endothelial cells. Circulation 143, 865–868 (2021). (PMID: 33405941789972010.1161/CIRCULATIONAHA.120.052824)
Conde, J. N., Schutt, W. R., Gorbunova, E. E. & Mackow, E. R. Recombinant ACE2 expression is required for SARS-CoV-2 to infect primary human endothelial cells and induce inflammatory and procoagulative responses. mBio 11, e03185–03120 (2020).
Krichel, B., Falke, S., Hilgenfeld, R., Redecke, L. & Uetrecht, C. Processing of the SARS-CoV pp1a/ab nsp7-10 region. Biochem. J. 477, 1009–1019 (2020). (PMID: 3208363810.1042/BCJ20200029)
Hadjadj, J. et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science 369, 718–724 (2020). (PMID: 32661059740263210.1126/science.abc6027)
Gordon, D. E. et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 583, 459–468 (2020). (PMID: 32353859743103010.1038/s41586-020-2286-9)
Körbelin, J. et al. A brain microvasculature endothelial cell-specific viral vector with the potential to treat neurovascular and neurological diseases. EMBO Mol. Med. 8, 609–625 (2016). (PMID: 27137490488885210.15252/emmm.201506078)
Ridder, D. A. et al. Brain endothelial TAK1 and NEMO safeguard the neurovascular unit. J. Exp. Med. 212, 1529–1549 (2015). (PMID: 26347470457783710.1084/jem.20150165)
Rothhammer, V. et al. Microglial control of astrocytes in response to microbial metabolites. Nature 557, 724–728 (2018). (PMID: 29769726642215910.1038/s41586-018-0119-x)
Welz, P. S. et al. FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation. Nature 477, 330–334 (2011). (PMID: 2180456410.1038/nature10273)
Mifflin, L., Ofengeim, D. & Yuan, J. Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target. Nat. Rev. Drug Discov. 19, 553–571 (2020). (PMID: 3266965810.1038/s41573-020-0071-y)
Villaseñor, R. et al. Trafficking of endogenous immunoglobulins by endothelial cells at the blood–brain barrier. Sci. Rep. 6, 25658 (2016). (PMID: 27149947485871910.1038/srep25658)
Martens, S., Hofmans, S., Declercq, W., Augustyns, K. & Vandenabeele, P. Inhibitors targeting RIPK1/RIPK3: old and new drugs. Trends Pharmacol. Sci. 41, 209–224 (2020). (PMID: 3203565710.1016/j.tips.2020.01.002)
Alarcon-Martinez, L. et al. Interpericyte tunnelling nanotubes regulate neurovascular coupling. Nature 585, 91–95 (2020). (PMID: 3278872610.1038/s41586-020-2589-x)
Gao, X. et al. Reduction of neuronal activity mediated by blood-vessel regression in the brain. Preprint at bioRxiv https://doi.org/10.1101/2020.09.15.262782 (2020).
Colmenero, I. et al. SARS-CoV-2 endothelial infection causes COVID-19 chilblains: histopathological, immunohistochemical and ultrastructural study of seven paediatric cases. Br. J. Dermatol. 183, 729–737 (2020). (PMID: 3256256710.1111/bjd.19327)
Yeung, M. L. et al. Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin–angiotensin system. Cell 184, 2212–2228 (2021). (PMID: 33713620792394110.1016/j.cell.2021.02.053)
Daly, J. L. et al. Neuropilin-1 is a host factor for SARS-CoV-2 infection. Science 370, 861–865 (2020). (PMID: 3308229410.1126/science.abd3072)
Zhang, J. et al. A systemic and molecular study of subcellular localization of SARS-CoV-2 proteins. Signal Transduct. Target. Ther. 5, 269 (2020). (PMID: 33203855767084310.1038/s41392-020-00372-8)
Miyamoto, S. Nuclear initiated NF-κB signaling: NEMO and ATM take center stage. Cell Res. 21, 116–130 (2011). (PMID: 2118785510.1038/cr.2010.179)
Arunachalam, P. S. et al. Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans. Science 369, 1210–1220 (2020). (PMID: 32788292766531210.1126/science.abc6261)
Wang, D. et al. Porcine epidemic diarrhea virus 3C-like protease regulates its interferon antagonism by cleaving NEMO. J. Virol. 90, 2090–2101 (2016). (PMID: 26656704473399610.1128/JVI.02514-15)
Zhu, X. et al. Porcine deltacoronavirus nsp5 inhibits interferon-beta production through the cleavage of NEMO. Virology 502, 33–38 (2017). (PMID: 2798478410.1016/j.virol.2016.12.005)
Chen, S. et al. Feline infectious peritonitis virus Nsp5 inhibits type I interferon production by cleaving NEMO at multiple sites. Viruses 12, 43 (2019). (PMID: 701973210.3390/v12010043)
Gareus, R. et al. Endothelial cell-specific NF-κB inhibition protects mice from atherosclerosis. Cell Metab. 8, 372–383 (2008). (PMID: 1904656910.1016/j.cmet.2008.08.016)
van Loo, G. et al. Inhibition of transcription factor NF-kB in the central nervous system ameliorates autoimmune encephalomyelitis in mice. Nat. Immunol. 7, 954–961 (2006). (PMID: 1689206910.1038/ni1372)
Meuwissen, M. E. & Mancini, G. M. Neurological findings in incontinentia pigmenti; a review. Eur. J. Med. Genet. 55, 323–331 (2012). (PMID: 2256488510.1016/j.ejmg.2012.04.007)
Kanberg, N. et al. Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19. Neurology 95, e1754–e1759 (2020). (PMID: 3254665510.1212/WNL.0000000000010111)
Senatorov, V. V. Jr. et al. Blood–brain barrier dysfunction in aging induces hyperactivation of TGFβ signaling and chronic yet reversible neural dysfunction. Sci. Transl. Med. 11, eaaw8283 (2019). (PMID: 3180188610.1126/scitranslmed.aaw8283)
Nampoothiri, S. et al. The hypothalamus as a hub for SARS-CoV-2 brain infection and pathogenesis. Preprint at bioRxiv https://doi.org/10.1101/2020.06.08.139329 (2020).
Schmidt-Supprian, M. et al. NEMO/IKKγ-deficient mice model incontinentia pigmenti. Mol. Cell 5, 981–992 (2000). (PMID: 1091199210.1016/S1097-2765(00)80263-4)
Luedde, T. et al. Deletion of NEMO/IKKγ in liver parenchymal cells causes steatohepatitis and hepatocellular carcinoma. Cancer Cell 11, 119–132 (2007). (PMID: 1729282410.1016/j.ccr.2006.12.016)
Ridder, D. A. et al. TAK1 in brain endothelial cells mediates fever and lethargy. J. Exp. Med. 208, 2615–2623 (2011). (PMID: 22143887324403110.1084/jem.20110398)
Newton, K., Sun, X. & Dixit, V. M. Kinase RIP3 is dispensable for normal NF-κBs, signaling by the B cell and T cell receptors, tumor necrosis factor receptor 1, and Toll-like receptors 2 and 4. Mol. Cell. Biol. 24, 1464–1469 (2004). (PMID: 1474936434419010.1128/MCB.24.4.1464-1469.2004)
Zelic, M. et al. RIPK1 activation mediates neuroinflammation and disease progression in multiple sclerosis. Cell Rep. 35, 109112 (2021). (PMID: 3397962210.1016/j.celrep.2021.1091128917516)
Wang, W. et al. RIP1 kinase drives macrophage-mediated adaptive immune tolerance in pancreatic cancer. Cancer Cell 34, 757–774 (2018). (PMID: 30423296683672610.1016/j.ccell.2018.10.006)
Qin, J. Y. et al. Systematic comparison of constitutive promoters and the doxycycline-inducible promoter. PLoS ONE 5, e10611 (2010). (PMID: 20485554286890610.1371/journal.pone.0010611)
Dogbevia, G. K. et al. Gene therapy decreases seizures in a model of incontinentia pigmenti. Ann. Neurol. 82, 93–104 (2017). (PMID: 2862823110.1002/ana.24981)
Korte, J., Mienert, J., Hennigs, J. K. & Korbelin, J. Inactivation of adeno-associated viral vectors by oxidant-based disinfectants. Hum. Gene Ther. 32, 771–781 (2021). (PMID: 3302332010.1089/hum.2020.120)
Dogbevia, G., Grasshoff, H., Othman, A., Penno, A. & Schwaninger, M. Brain endothelial specific gene therapy improves experimental Sandhoff disease. J. Cereb. Blood Flow Metab. 40, 1338–1350 (2020). (PMID: 3135790210.1177/0271678X19865917)
Bojkova, D. et al. Proteomics of SARS-CoV-2-infected host cells reveals therapy targets. Nature 583, 469–472 (2020). (PMID: 3240833610.1038/s41586-020-2332-7)
Hoehl, S. et al. Evidence of SARS-CoV-2 infection in returning travelers from Wuhan, China. N. Engl. J. Med. 382, 1278–1280 (2020). (PMID: 32069388712174910.1056/NEJMc2001899)
Pfefferle, S. et al. Complete genome sequence of a SARS-CoV-2 strain isolated in northern Germany. Microbiol. Resour. Announc. 9, e00520-20 (2020).
Fan, H. C., Fu, G. K. & Fodor, S. P. Expression profiling. Combinatorial labeling of single cells for gene expression cytometry. Science 347, 1258367 (2015). (PMID: 2565725310.1126/science.1258367)
Munawar, A. et al. Elapid snake venom analyses show the specificity of the peptide composition at the level of genera Naja and Notechis. Toxins 6, 850–868 (2014). (PMID: 24590383396836510.3390/toxins6030850)
Cox, J. & Mann, M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat. Biotechnol. 26, 1367–1372 (2008). (PMID: 10.1038/nbt.151119029910)
Allan, C. et al. OMERO: flexible, model-driven data management for experimental biology. Nat. Methods 9, 245–253 (2012). (PMID: 22373911343782010.1038/nmeth.1896)
Chozinski, T. J. et al. Expansion microscopy with conventional antibodies and fluorescent proteins. Nat. Methods 13, 485–488 (2016). (PMID: 27064647492914710.1038/nmeth.3833)
Gaehtgens, P. Flow of blood through narrow capillaries: rheological mechanisms determining capillary hematocrit and apparent viscosity. Biorheology 17, 183–189 (1980). (PMID: 740734810.3233/BIR-1980-171-220)
Hunziker, O., Abdel’Al, S. & Schulz, U. The aging human cerebral cortex: a stereological characterization of changes in the capillary net. J. Gerontol. 34, 345–350 (1979). (PMID: 42976710.1093/geronj/34.3.345)
Jiang, Y. et al. Cerebral angiogenesis ameliorates pathological disorders in Nemo-deficient mice with small-vessel disease. J. Cereb. Blood Flow Metab. 41, 219–235 (2021). (PMID: 3215122310.1177/0271678X20910522)
معلومات مُعتمدة: 810331 International ERC_ European Research Council
المشرفين على المادة: 0 (Intracellular Signaling Peptides and Proteins)
0 (NEMO protein, mouse)
EC 3.4.22.28 (Coronavirus 3C Proteases)
تواريخ الأحداث: Date Created: 20211022 Date Completed: 20211108 Latest Revision: 20230207
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC8553622
DOI: 10.1038/s41593-021-00926-1
PMID: 34675436
قاعدة البيانات: MEDLINE
الوصف
تدمد:1546-1726
DOI:10.1038/s41593-021-00926-1