{"doi":"10.1016/j.stem.2023.12.012","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.","journal":"Cell stem cell","year":2024,"id":416603,"datarank":3.3304099777852185,"base_score":4.7535901911063645,"endowment":4.7535901911063645,"self_citation_contribution":0.7130385286659547,"citation_network_contribution":2.617371449119264,"self_endowment_contribution":0.7130385286659547,"citer_contribution":2.617371449119264,"corpus_percentile":null,"corpus_rank":null,"citation_count":115,"citer_count":91,"citers_with_citation_signal":63,"citers_with_endowment":63,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.968,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":109216,"name":"Tae Wan Kim","orcid":"0000-0002-0831-6881","position":1,"is_corresponding":false},{"id":109208,"name":"Yuling Han","orcid":"0000-0002-6805-4094","position":2,"is_corresponding":false},{"id":105620,"name":"Manoj S. 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