Abstract
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 (Mpro) cleaves NEMO, the essential modulator of nuclear factor-κB. By ablating NEMO, Mpro 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 Mpro-induced microvascular pathology. Our data suggest RIPK as a potential therapeutic target to treat the neuropathology of COVID-19.
Original language | English |
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Journal | Nature Neuroscience |
Volume | 24 |
Issue number | 11 |
Pages (from-to) | 1522-1533 |
Number of pages | 12 |
ISSN | 1097-6256 |
DOIs | |
Publication status | Published - 11.2021 |
Research Areas and Centers
- Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)
Coronavirus related work
- Research on SARS-CoV-2 / COVID-19
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Perfood Research Award 2021
Wenzel, Jan (Award Recipient), Lampe, Josephine (Award Recipient) & Müller-Fielitz, Helge (Award Recipient), 21.11.2021
Prize: Awards of the University of Luebeck