Neuroproteomic Analysis after SARS-CoV-2 Infection Reveals Overrepresented Neurodegeneration Pathways and Disrupted Metabolic Pathways.

Publication date: Oct 30, 2023

Besides respiratory illness, SARS-CoV-2, the causative agent of COVID-19, leads to neurological symptoms. The molecular mechanisms leading to neuropathology after SARS-CoV-2 infection are sparsely explored. SARS-CoV-2 enters human cells via different receptors, including ACE-2, TMPRSS2, and TMEM106B. In this study, we used a human-induced pluripotent stem cell-derived neuronal model, which expresses ACE-2, TMPRSS2, TMEM106B, and other possible SARS-CoV-2 receptors, to evaluate its susceptibility to SARS-CoV-2 infection. The neurons were exposed to SARS-CoV-2, followed by RT-qPCR, immunocytochemistry, and proteomic analyses of the infected neurons. Our findings showed that SARS-CoV-2 infects neurons at a lower rate than other human cells; however, the virus could not replicate or produce infectious virions in this neuronal model. Despite the aborted SARS-CoV-2 replication, the infected neuronal nuclei showed irregular morphology compared to other human cells. Since cytokine storm is a significant effect of SARS-CoV-2 infection in COVID-19 patients, in addition to the direct neuronal infection, the neurons were treated with pre-conditioned media from SARS-CoV-2-infected lung cells, and the neuroproteomic changes were investigated. The limited SARS-CoV-2 infection in the neurons and the neurons treated with the pre-conditioned media showed changes in the neuroproteomic profile, particularly affecting mitochondrial proteins and apoptotic and metabolic pathways, which may lead to the development of neurological complications. The findings from our study uncover a possible mechanism behind SARS-CoV-2-mediated neuropathology that might contribute to the lingering effects of the virus on the human brain.

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Concepts Keywords
Aborted apoptosis
Immunocytochemistry COVID-19
Neurons COVID-19
Neuropathology Culture Media, Conditioned
Tmem106b Culture Media, Conditioned
Humans
mass spectrometry
Membrane Proteins
Membrane Proteins
metabolism
Nerve Tissue Proteins
Nerve Tissue Proteins
NeuroCOVID
neurodegeneration
Proteomics
proteomics
SARS-CoV-2
SARS-CoV-2

Semantics

Type Source Name
disease MESH SARS-CoV-2 Infection
pathway REACTOME SARS-CoV-2 Infection
pathway KEGG Metabolic pathways
disease IDO cell
disease IDO susceptibility
disease IDO replication
disease MESH cytokine storm
disease MESH infection
disease MESH complications
disease VO Canada
pathway KEGG Apoptosis
disease MESH pneumonia
drug DRUGBANK Coenzyme M
disease MESH seizures
disease MESH encephalitis
disease MESH stroke
disease VO organ
disease MESH Parkinson’s disease
disease MESH delirium
disease MESH venous thrombosis
disease MESH meningoencephalitis
disease MESH syndrome
disease MESH myelitis
disease MESH posterior reversible encephalopathy syndrome
disease MESH morbidity
disease VO volume
disease MESH cognitive dysfunction
disease MESH peripheral nervous system disorders
disease MESH migraine
disease MESH movement disorders
disease MESH mental disorders
disease MESH sensory disorders
disease MESH encephalopathy
disease MESH Alzheimer’s disease
disease MESH multiple sclerosis
disease IDO host
disease MESH death
drug DRUGBANK Pentaerythritol tetranitrate
disease VO protocol
drug DRUGBANK Doxycycline
drug DRUGBANK Cobalt chloride
pathway KEGG Viral replication
drug DRUGBANK Puromycin
disease VO population
disease IDO production
disease VO dose
disease IDO infectivity
disease VO USA
disease VO gene
drug DRUGBANK Sodium lauryl sulfate
disease IDO assay
drug DRUGBANK Ademetionine
drug DRUGBANK Silicon dioxide
drug DRUGBANK Flunarizine
disease MESH dissociation
drug DRUGBANK L-Cysteine
disease VO ANOVA
disease MESH neuroinflammation
disease IDO symptom
drug DRUGBANK Pidolic Acid

Original Article

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