SARS-CoV-2 infection causes dopaminergic neuron senescence

2024/01/17 by Liuliu Yang, Tae Wan Kim, Yuling Han +25 · 1 voice · 117 citations
Medicine · Neuroscience · #Biology #Cell biology #Dopamine #Dopaminergic #Embryonic stem cell #Genetics #Immunology #Induced pluripotent stem cell #Long-Term Effects of COVID-19 #Neuroinflammation and Neurodegeneration Mechanisms #Neuroprotection #Neuroscience #Senescence #Substantia nigra #Tryptophan and brain disorders

paper · doi:10.1016/j.stem.2023.12.012

published in Cell stem cell 31(2), 196-211.e6 (Elsevier BV)

openalex publication_date 2024/01/17 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/06

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.

Citations

• Lifting the mask on neurological manifestations of COVID-19

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Discussions

• @castltrastondrs.bsky.social Sleep Dude here.... The intersection of clinical Neurobiology the effects of Cøvid shouldn't be underestimated. People have really missed the Dopa senescence paper in i [bsky, 23 points, 2 comments]

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