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Post by Nadica (She/Her) on Jul 7, 2024 5:46:49 GMT
SARS-CoV-2 infection causes dopaminergic neuron senescence - Published Jan 17, 2024Highlights •hPSC-derived DA neurons are susceptible to SARS-CoV-2 infection •SARS-CoV-2 infection of DA neurons triggers cellular senescence response •Several FDA-approved drugs were identified to rescue senescence of DA neurons •Cellular senescence was found in substantia nigra tissues of COVID-19 patients Summary 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. Graphical abstract
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