Proteomics

Dataset Information

0

SARS-CoV-2 Spike Protein in the Skull-Meninges-Brain Axis


ABSTRACT: COVID-19 has been associated with a variety of neurological symptoms, including brain fog and brain tissue loss. This raises concerns about the virus's acute and potential chronic impacts on the brain. Using whole mouse and human tissue clearing, we determined all potential tissues targeted by the SARS-CoV-2 and showed that the spike protein accumulates in the skull-meninges-brain axis in both mice and humans. Injection of the spike protein into the mouse skull alone was sufficient to cause cell death in the brain. Notably, we found spike protein in the skull of ~60% of deceased people who had COVID-19 in the past. Mass spectrometry-based proteomics in mice and humans revealed dysregulated inflammatory and vascular pathways throughout tissues in the skull-meninges-brain axis. Overall, SARS-CoV-2 spike protein accumulation in the CNS borders might be involved in the immediate and long-term consequences in the brain parenchyma, and this may present diagnostic and therapeutic opportunities.

INSTRUMENT(S): timsTOF SCP

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Brain, Bone Marrow

SUBMITTER: Ali Erturk  

LAB HEAD: Ali Erturk

PROVIDER: PXD050384 | Pride | 2024-12-02

REPOSITORIES: pride

Dataset's files

Source:
Action DRS
Brain_Infection_RealVirus.zip Other
COVID_Human_Brain.zip Other
COVID_Human_Brain_LCM.zip Other
COVID_Human_Meninges.zip Other
COVID_Human_Skull.zip Other
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Publications

Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19.

Rong Zhouyi Z   Mai Hongcheng H   Ebert Gregor G   Kapoor Saketh S   Puelles Victor G VG   Czogalla Jan J   Hu Senbin S   Su Jinpeng J   Prtvar Danilo D   Singh Inderjeet I   Schädler Julia J   Delbridge Claire C   Steinke Hanno H   Frenzel Hannah H   Schmidt Katja K   Braun Christian C   Bruch Gina G   Ruf Viktoria V   Ali Mayar M   Sühs Kurt-Wolfram KW   Nemati Mojtaba M   Hopfner Franziska F   Ulukaya Selin S   Jeridi Denise D   Mistretta Daniele D   Caliskan Özüm Sehnaz ÖS   Wettengel Jochen Martin JM   Cherif Fatma F   Kolabas Zeynep Ilgin ZI   Molbay Müge M   Horvath Izabela I   Zhao Shan S   Krahmer Natalie N   Yildirim Ali Önder AÖ   Ussar Siegfried S   Herms Jochen J   Huber Tobias B TB   Tahirovic Sabina S   Schwarzmaier Susanne M SM   Plesnila Nikolaus N   Höglinger Günter G   Ondruschka Benjamin B   Bechmann Ingo I   Protzer Ulrike U   Elsner Markus M   Bhatia Harsharan Singh HS   Hellal Farida F   Ertürk Ali A  

Cell host & microbe 20241129 12


SARS-CoV-2 infection is associated with long-lasting neurological symptoms, although the underlying mechanisms remain unclear. Using optical clearing and imaging, we observed the accumulation of SARS-CoV-2 spike protein in the skull-meninges-brain axis of human COVID-19 patients, persisting long after viral clearance. Further, biomarkers of neurodegeneration were elevated in the cerebrospinal fluid from long COVID patients, and proteomic analysis of human skull, meninges, and brain samples revea  ...[more]

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