SARS-CoV-2 infection causes dopaminergic neuron senescence Journal Article

   


Authors: Yang, L.; Kim, T. W.; Han, Y.; Nair, M. S.; Harschnitz, O.; Zhu, J.; Wang, P.; Koo, S. Y.; Lacko, L. A.; Chandar, V.; Bram, Y.; Zhang, T.; Zhang, W.; He, F.; Pan, C.; Wu, J.; Huang, Y.; Evans, T.; van der Valk, P.; Titulaer, M. J.; Spoor, J. K. H.; Furler O'Brien, R. L.; Bugiani, M.; D.J. Van de Berg, W.; Schwartz, R. E.; Ho, D. D.; Studer, L.; Chen, S.
Article Title: SARS-CoV-2 infection causes dopaminergic neuron senescence
Abstract: COVID-19 patients commonly present with signs of central nervous system and/or peripheral nervous system dysfunction. Here, we show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively susceptible and permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection of DA neurons triggers an inflammatory and cellular senescence response. High-throughput screening in hPSC-derived DA neurons identified several FDA-approved drugs that can rescue the cellular senescence phenotype by preventing SARS-CoV-2 infection. We also identified the inflammatory and cellular senescence signature and low levels of SARS-CoV-2 transcripts in human substantia nigra tissue of COVID-19 patients. Furthermore, we observed reduced numbers of neuromelanin+ and tyrosine-hydroxylase (TH)+ DA neurons and fibers in a cohort of severe COVID-19 patients. Our findings demonstrate that hPSC-derived DA neurons are susceptible to SARS-CoV-2, identify candidate neuroprotective drugs for COVID-19 patients, and suggest the need for careful, long-term monitoring of neurological problems in COVID-19 patients. © 2023 The Author(s)
Keywords: adult; controlled study; human tissue; human cell; nonhuman; phenotype; reverse transcription polymerase chain reaction; inflammation; cohort analysis; high throughput screening; central nervous system; tyrosine 3 monooxygenase; mesencephalon; pluripotent stem cell; pluripotent stem cells; senescence; cell aging; dopamine; dopaminergic nerve cell; peripheral nervous system; neuroprotection; paraneoplastic cerebellar degeneration; dopaminergic neurons; human pluripotent stem cells; substantia nigra; humans; human; male; female; article; neuromelanin; dopaminergic neuron; severe acute respiratory syndrome coronavirus 2; coronavirus disease 2019; covid-19; sars-cov-2; paraneoplastic neurological syndrome
Journal Title: Cell Stem Cell
Volume: 31
Issue: 2
ISSN: 1934-5909
Publisher: Cell Press  
Date Published: 2024-02-01
Start Page: 196
End Page: 211.e6
Language: English
DOI: 10.1016/j.stem.2023.12.012
PUBMED: 38237586
PROVIDER: scopus
PMCID: PMC10843182
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85183491822&doi=10.1016%2fj.stem.2023.12.012&partnerID=40&md5=979397d0f79e29affe4af98627a233e8
Notes: Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding author is Lorenz Studer -- Source: Scopus
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MSK Authors
  1. Lorenz Studer
    220 Studer
  2. Taewan Kim
    11 Kim
  3. So Yeon Koo
    5 Koo
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