{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T03:54:39Z","timestamp":1772078079180,"version":"3.50.1"},"reference-count":76,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,30]],"date-time":"2021-10-30T00:00:00Z","timestamp":1635552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is primarily responsible for coronavirus disease (COVID-19) and it is characterized by respiratory illness with fever and dyspnea. Severe vascular problems and several other manifestations, including neurological ones, have also been frequently reported, particularly in the great majority of \u201clong hauler\u201d patients. SARS-CoV-2 infects and replicates in lung epithelial cells, while dysfunction of endothelial and neuronal brain cells has been observed in the absence of productive infection. It has been shown that the Spike protein can interact with specific cellular receptors, supporting both viral entry and cellular dysfunction. It is thus clear that understanding how and when these receptors are regulated, as well as how much they are expressed would help in unveiling the multifaceted aspects of this disease. Here, we show that SH-SY5Y neuroblastoma cells express three important cellular surface molecules that interact with the Spike protein, namely ACE2, TMPRSS2, and NRP1. Their levels increase when cells are treated with retinoic acid (RA), a commonly used agent known to promote differentiation. This increase matched the higher levels of receptors observed on HUVEC (primary human umbilical vein endothelial cells). We also show by confocal imaging that replication-defective pseudoviruses carrying the SARS-CoV-2 Spike protein can infect differentiated and undifferentiated SH-SY5Y, and HUVEC cells, although with different efficiencies. Neuronal cells and endothelial cells are potential targets for SARS-CoV-2 infection and the interaction of the Spike viral protein with these cells may cause their dysregulation. Characterizing RNA and protein expression tempo, mode, and levels of different SARS-CoV-2 receptors on both cell subpopulations may have clinical relevance for the diagnosis and treatment of COVID-19-infected subjects, including long hauler patients with neurological manifestations.<\/jats:p>","DOI":"10.3390\/v13112193","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T22:14:52Z","timestamp":1635891292000},"page":"2193","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Comparison of SARS-CoV-2 Receptors Expression in Primary Endothelial Cells and Retinoic Acid-Differentiated Human Neuronal Cells"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8720-090X","authenticated-orcid":false,"given":"Francesca","family":"Benedetti","sequence":"first","affiliation":[{"name":"Institute of Human Virology and Global Virus Network Center, Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5911-6997","authenticated-orcid":false,"given":"Giovannino","family":"Silvestri","sequence":"additional","affiliation":[{"name":"Institute of Human Virology and Global Virus Network Center, Department of Medicine, School of Medicine, University of Maryland, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3819-5520","authenticated-orcid":false,"given":"Carla","family":"Mavian","sequence":"additional","affiliation":[{"name":"Emerging Pathogens Institute, Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Weichseldorfer","sequence":"additional","affiliation":[{"name":"Institute of Human Virology and Global Virus Network Center, Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arshi","family":"Munawwar","sequence":"additional","affiliation":[{"name":"Institute of Human Virology and Global Virus Network Center, Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0144-7878","authenticated-orcid":false,"given":"Melanie N.","family":"Cash","sequence":"additional","affiliation":[{"name":"Emerging Pathogens Institute, Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"Dulcey","sequence":"additional","affiliation":[{"name":"Emerging Pathogens Institute, Department of Environmental and Global Health, College of Medicine, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy Y.","family":"Vittor","sequence":"additional","affiliation":[{"name":"Emerging Pathogens Institute, Department of Environmental and Global Health, College of Medicine, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Ciccozzi","sequence":"additional","affiliation":[{"name":"Medical Statistic and Molecular Epidemiology Unit, University of Biomedical Campus, 00128 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Salemi","sequence":"additional","affiliation":[{"name":"Emerging Pathogens Institute, Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga S.","family":"Latinovic","sequence":"additional","affiliation":[{"name":"Institute of Human Virology and Global Virus Network Center, Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5576-5770","authenticated-orcid":false,"given":"Davide","family":"Zella","sequence":"additional","affiliation":[{"name":"Institute of Human Virology and Global Virus Network Center, Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/s41586-021-03570-8","article-title":"COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets","volume":"595","author":"Delorey","year":"2021","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/s41586-021-03569-1","article-title":"A molecular single-cell lung atlas of lethal COVID-19","volume":"595","author":"Melms","year":"2021","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1056\/NEJMc2008597","article-title":"Neurologic Features in Severe SARS-CoV-2 Infection","volume":"382","author":"Helms","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1056\/NEJMc2011400","article-title":"Multiorgan and Renal Tropism of SARS-CoV-2","volume":"383","author":"Puelles","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/s41421-021-00249-2","article-title":"SARS-CoV-2 cell tropism and multiorgan infection","volume":"7","author":"Liu","year":"2021","journal-title":"Cell Discov."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.3389\/fimmu.2020.02094","article-title":"PI3K\u03b4 Inhibition as a Potential Therapeutic Target in COVID-19","volume":"11","author":"Palma","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"579","author":"Zhou","year":"2020","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1126\/science.abc6156","article-title":"How does SARS-CoV-2 cause COVID-19?","volume":"369","author":"Matheson","year":"2020","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"11727","DOI":"10.1073\/pnas.2003138117","article-title":"Cell entry mechanisms of SARS-CoV-2","volume":"117","author":"Shang","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Xu, J., and Lazartigues, E. (2020). Expression of ACE2 in Human Neurons Supports the Neuro-Invasive Potential of COVID-19 Virus. Cell. Mol. Neurobiol.","DOI":"10.1007\/s10571-020-00915-1"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1002\/path.1570","article-title":"Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis","volume":"203","author":"Hamming","year":"2004","journal-title":"J. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/nm1267","article-title":"A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus\u2013induced lung injury","volume":"11","author":"Kuba","year":"2005","journal-title":"Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Caccuri, F., Bugatti, A., Zani, A., De Palma, A., Di Silvestre, D., Manocha, E., Filippini, F., Messali, S., Chiodelli, P., and Campisi, G. (2021). SARS-CoV-2 Infection Remodels the Phenotype and Promotes Angiogenesis of Primary Human Lung Endothelial. Cells Microorg., 9.","DOI":"10.3390\/microorganisms9071438"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1126\/science.abd2985","article-title":"Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity","volume":"370","author":"Ojha","year":"2020","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1126\/science.abd3072","article-title":"Neuropilin-1 is a host factor for SARS-CoV-2 infection","volume":"370","author":"Daly","year":"2020","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e14","DOI":"10.1016\/S2666-5247(20)30004-5","article-title":"Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: An observational study","volume":"1","author":"Chu","year":"2020","journal-title":"Lancet Microbe"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1038\/s41422-020-0390-x","article-title":"SARS-CoV-2 infects human neural progenitor cells and brain organoids","volume":"30","author":"Zhang","year":"2020","journal-title":"Cell Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"147344","DOI":"10.1016\/j.brainres.2021.147344","article-title":"Susceptibility of neuroblastoma and glioblastoma cell lines to SARS-CoV-2 infection","volume":"1758","author":"Bielarz","year":"2021","journal-title":"Brain Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1001\/jamaneurol.2020.1127","article-title":"Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China","volume":"77","author":"Mao","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"The Lancet Psychiatry (2021). COVID-19 and mental health. Lancet Psychiatry, 8, 87.","DOI":"10.1016\/S2215-0366(21)00005-5"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1056\/NEJMoa2015432","article-title":"Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19","volume":"383","author":"Ackermann","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/S0140-6736(20)30937-5","article-title":"Endothelial cell infection and endotheliitis in COVID-19","volume":"395","author":"Varga","year":"2020","journal-title":"Lancet"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1021\/acscentsci.0c01537","article-title":"CD209L\/L-SIGN and CD209\/DC-SIGN Act as Receptors for SARS-CoV-2","volume":"7","author":"Amraei","year":"2021","journal-title":"ACS Cent. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1038\/s41419-020-03252-9","article-title":"A cross-talk between epithelium and endothelium mediates human alveolar-capillary injury during SARS-CoV-2 infection","volume":"11","author":"Wang","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"106829","DOI":"10.1016\/j.vph.2021.106829","article-title":"Endothelial cells and SARS-CoV-2: An intimate relationship","volume":"137","author":"Barbosa","year":"2021","journal-title":"Vasc. Pharm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1111\/bjd.19327","article-title":"SARS-CoV-2 endothelial infection causes COVID-19 chilblains: Histopathological, immunohistochemical and ultrastructural study of seven paediatric cases","volume":"183","author":"Colmenero","year":"2020","journal-title":"Br. J. Derm."},{"key":"ref_29","first-page":"1","article-title":"Endothelial activation and dysfunction in COVID-19: From basic mechanisms to potential therapeutic approaches","volume":"5","author":"Jin","year":"2020","journal-title":"Signal. Transduct. Target. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"103182","DOI":"10.1016\/j.ebiom.2020.103182","article-title":"SARS-CoV-2 leads to a small vessel endotheliitis in the heart","volume":"63","author":"Maccio","year":"2021","journal-title":"EBioMedicine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1111\/jth.14768","article-title":"Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia","volume":"18","author":"Tang","year":"2020","journal-title":"J. Thromb. Haemost."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/s41577-020-0343-0","article-title":"Carmeliet, COVID-19: The vasculature unleashed","volume":"20","author":"Teuwen","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_33","first-page":"2643","article-title":"Morphology and growth, tumorigenicity, and cytogenetics of human neuroblastoma cells in continuous culture","volume":"33","author":"Biedler","year":"1973","journal-title":"Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.neuro.2008.11.001","article-title":"Effects of all-trans-retinoic acid on human SH-SY5Y neuroblastoma as in vitro model in neurotoxicity research","volume":"30","author":"Cheung","year":"2009","journal-title":"NeuroToxicology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1002\/jnr.20976","article-title":"Differentiation of a human neuroblastoma into neuron-like cells increases their susceptibility to transduction by herpesviral vectors","volume":"84","author":"Lim","year":"2006","journal-title":"J. Neurosci. Res."},{"key":"ref_36","first-page":"219","article-title":"Phenotypic diversification in human neuroblastoma cells: Expression of distinct neural crest lineages","volume":"49","author":"Ciccarone","year":"1989","journal-title":"Cancer Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1002\/ijc.2910280509","article-title":"Phenotypic changes of human neuroblastoma cells in culture induced by 12-O-tetradecanoyl-phorbol-13-acetate","volume":"28","author":"Odelstad","year":"1981","journal-title":"Int. J. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1016\/j.jpedsurg.2008.01.007","article-title":"All-trans retinoic acid arrests neuroblastoma cells in a dormant state. Subsequent nerve growth factor\/brain-derived neurotrophic factor treatment adds modest benefit","volume":"43","author":"Cernaianu","year":"2008","journal-title":"J. Pediatr. Surg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.neulet.2008.07.079","article-title":"Dibutyryl cyclic AMP induces differentiation of human neuroblastoma SH-SY5Y cells into a noradrenergic phenotype","volume":"443","author":"Kume","year":"2008","journal-title":"Neurosci. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.ijdevneu.2008.11.007","article-title":"Extracellular guanosine and GTP promote expression of differentiation markers and induce S-phase cell-cycle arrest in human SH-SY5Y neuroblastoma cells","volume":"27","author":"Guarnieri","year":"2009","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1016\/j.peptides.2007.03.001","article-title":"Staurosporine differentiation of NPFF2 receptor-transfected SH-SY5Y neuroblastoma cells induces selectivity of NPFF activity towards opioid receptors","volume":"28","author":"Mollereau","year":"2007","journal-title":"Peptides"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.brainres.2007.04.015","article-title":"Transcriptional regulation of polysialylated neural cell adhesion molecule expression by NMDA receptor activation in retinoic acid-differentiated SH-SY5Y neuroblastoma cultures","volume":"1154","author":"Singh","year":"2007","journal-title":"Brain Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/0045-6039(84)90038-1","article-title":"Retinoic acid-induced differentiation of cultured human neuroblastoma cells: A comparison with phorbolester-induced differentiation","volume":"14","author":"Ruusala","year":"1984","journal-title":"Cell Differ."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1002\/neu.20241","article-title":"Role of all-trans retinoic acid in neurite outgrowth and axonal elongation","volume":"66","author":"McNeill","year":"2006","journal-title":"J. Neurobiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1002\/jnr.10641","article-title":"Presenilin 1 mediates retinoic acid-induced differentiation of SH-SY5Y cells through facilitation of Wnt signaling","volume":"73","author":"Uemura","year":"2003","journal-title":"J. Neurosci. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1002\/(SICI)1097-4652(200003)182:3<421::AID-JCP13>3.0.CO;2-2","article-title":"Participation of type II protein kinase A in the retinoic acid-induced growth inhibition of SH-SY5Y human neuroblastoma cells","volume":"182","author":"Kim","year":"2000","journal-title":"J. Cell Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1021\/acs.jproteome.0c00614","article-title":"Temporal Proteomic Profiling of SH-SY5Y Differentiation with Retinoic Acid Using FAIMS and Real-Time Searching","volume":"20","author":"Zhang","year":"2021","journal-title":"J. Proteome Res."},{"key":"ref_48","first-page":"53193","article-title":"Differentiation of the SH-SY5Y Human Neuroblastoma Cell Line. Journal of visualized experiments","volume":"108","author":"Shipley","year":"2016","journal-title":"JoVE"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1177\/1087057115625190","article-title":"Characterization of Differentiated SH-SY5Y as Neuronal Screening Model Reveals Increased Oxidative Vulnerability","volume":"21","author":"Forster","year":"2016","journal-title":"J. Biomol. Screen."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1007\/s11064-015-1743-6","article-title":"Morphological Differentiation Towards Neuronal Phenotype of SH-SY5Y Neuroblastoma Cells by Estradiol, Retinoic Acid and Cholesterol","volume":"41","author":"Teppola","year":"2016","journal-title":"Neurochem. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/978-1-62703-640-5_2","article-title":"Considerations for the use of SH-SY5Y neuroblastoma cells in neurobiology","volume":"1078","author":"Kovalevich","year":"2013","journal-title":"Methods Mol. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.conb.2021.04.005","article-title":"Neurovascular crosstalk coordinates the central nervous system development","volume":"69","author":"Peguera","year":"2021","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1126\/science.aad3839","article-title":"Oligodendrocyte precursors migrate along vasculature in the developing nervous system","volume":"351","author":"Tsai","year":"2016","journal-title":"Science"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.cell.2020.04.004","article-title":"Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2","volume":"181","author":"Monteil","year":"2020","journal-title":"Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e187","DOI":"10.1111\/jdv.16970","article-title":"SARS-CoV-2 spike protein is present in both endothelial and eccrine cells of a chilblain-like skin lesion","volume":"35","author":"Gambichler","year":"2021","journal-title":"J. Eur. Acad. Derm. Venereol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1161\/CIRCRESAHA.121.318902","article-title":"SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE 2","volume":"128","author":"Lei","year":"2021","journal-title":"Circ. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"151682","DOI":"10.1016\/j.anndiagpath.2020.151682","article-title":"Endothelial cell damage is the central part of COVID-19 and a mouse model induced by injection of the S1 subunit of the spike protein","volume":"51","author":"Nuovo","year":"2021","journal-title":"Ann. Diagn. Pathol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.stem.2020.10.001","article-title":"SARS-CoV-2 Infects the Brain Choroid Plexus and Disrupts the Blood-CSF Barrier in Human Brain Organoids","volume":"27","author":"Pellegrini","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.stemcr.2021.02.005","article-title":"Revealing Tissue-Specific SARS-CoV-2 Infection and Host Responses using Human Stem Cell-Derived Lung and Cerebral Organoids","volume":"16","author":"Tiwari","year":"2021","journal-title":"Stem Cell Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/j.stem.2020.09.016","article-title":"Human Pluripotent Stem Cell-Derived Neural Cells and Brain Organoids Reveal SARS-CoV-2 Neurotropism Predominates in Choroid Plexus Epithelium","volume":"27","author":"Jacob","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/S2215-0366(21)00084-5","article-title":"6-month neurological and psychiatric outcomes in 236\u2009379 survivors of COVID-19: A retrospective cohort study using electronic health records","volume":"8","author":"Taquet","year":"2021","journal-title":"Lancet Psychiatry"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e2021450118","DOI":"10.1073\/pnas.2021450118","article-title":"Targeting transcriptional regulation of SARS-CoV-2 entry factors ACE2 and TMPRSS2","volume":"118","author":"Qiao","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Niland, S., and Eble, J.A. (2019). Neuropilins in the Context of Tumor Vasculature. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030639"},{"key":"ref_64","first-page":"4221","article-title":"Neuropilin-1 as a new potential SARS-CoV-2 infection mediator implicated in the neurologic features and central nervous system involvement of COVID-19","volume":"22","author":"Davies","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41419-019-1338-2","article-title":"Neuropilin-1-mediated pruning of corticospinal tract fibers is required for motor recovery after spinal cord injury","volume":"10","author":"Nakanishi","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Salehi, P., Ge, M.X., Gundimeda, U., Michelle Baum, L., Lael Cantu, H., Lavinsky, J., Tao, L., Myint, A., Cruz, C., and Wang, J. (2017). Role of Neuropilin-1\/Semaphorin-3A signaling in the functional and morphological integrity of the cochlea. PLoS Genet., 13.","DOI":"10.1371\/journal.pgen.1007048"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1038\/nrn.2017.85","article-title":"Neuronal cell-type classification: Challenges, opportunities and the path forward","volume":"18","author":"Zeng","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.neuron.2020.04.018","article-title":"Extraction of Distinct Neuronal Cell Types from within a Genetically Continuous Population","volume":"107","author":"Kim","year":"2020","journal-title":"Neuron"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.humpath.2018.06.030","article-title":"Neuropilin-1 (NRP-1) upregulated by IL-6\/STAT3 signaling contributes to invasion in pancreatic neuroendocrine neoplasms","volume":"81","author":"Yang","year":"2018","journal-title":"Hum. Pathol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"10941","DOI":"10.1038\/s41598-017-11287-w","article-title":"Neuropilin-1 is upregulated by Wnt\/\u03b2-catenin signaling and is important for mammary stem cells","volume":"7","author":"Liu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3892","DOI":"10.1038\/onc.2009.247","article-title":"Macrophage-derived IL-1beta stimulates Wnt signaling and growth of colon cancer cells: A crosstalk interrupted by vitamin D3","volume":"28","author":"Kaler","year":"2009","journal-title":"Oncogene"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"59","DOI":"10.3389\/fcell.2019.00059","article-title":"Neuronal Migration Generates New Populations of Neurons That Develop Unique Connections, Physiological Properties and Pathologies","volume":"7","author":"Fritzsch","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1002\/acn3.51350","article-title":"Persistent neurologic symptoms and cognitive dysfunction in non-hospitalized Covid-19 \u201clong haulers\u201d","volume":"8","author":"Graham","year":"2021","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1002\/alz.12255","article-title":"The chronic neuropsychiatric sequelae of COVID-19: The need for a prospective study of viral impact on brain functioning","volume":"17","author":"Snyder","year":"2021","journal-title":"Alzheimers Dement."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.brainres.2010.03.102","article-title":"Comparison between proliferative and neuron-like SH-SY5Y cells as an in vitro model for Parkinson disease studies","volume":"1337","author":"Lopes","year":"2010","journal-title":"Brain Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"prot095026","DOI":"10.1101\/pdb.prot095026","article-title":"Constructing a Standard Curve for Real-Time Polymerase Chain Reaction (PCR) Experiments","volume":"10","author":"Green","year":"2018","journal-title":"Cold Spring Harb. 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