{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:19:50Z","timestamp":1790637590014,"version":"4.1.0"},"reference-count":47,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Brain, Behavior, and Immunity"],"published-print":{"date-parts":[[2023,2]]},"DOI":"10.1016\/j.bbi.2022.12.017","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T02:16:25Z","timestamp":1671416185000},"page":"302-308","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":25,"special_numbering":"C","title":["Substance P and Prokineticin-2 are overexpressed in olfactory neurons and play differential roles in persons with persistent post-COVID-19 olfactory dysfunction"],"prefix":"10.1016","volume":"108","author":[{"given":"Tommaso","family":"Schirinzi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Lattanzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Maftei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piergiorgio","family":"Grillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri","family":"Zenuni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Boffa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Albanese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Simonetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Bovenzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Maurizi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Loccisano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Vincenzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Greco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Di Girolamo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola B.","family":"Mercuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco M.","family":"Passali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Severini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bbi.2022.12.017_b0005","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-021-24469-y","article-title":"Prokineticin-2 prevents neuronal cell deaths in a model of traumatic brain injury","volume":"12","author":"Bao","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.bbi.2022.12.017_b0010","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2020.00145","article-title":"Neurodegeneration-Associated Proteins in Human Olfactory Neurons Collected by Nasal Brushing","volume":"14","author":"Brozzetti","year":"2020","journal-title":"Front. Neurosci."},{"key":"10.1016\/j.bbi.2022.12.017_b0015","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1177\/1073858420956905","article-title":"Anosmia in COVID-19: Underlying Mechanisms and Assessment of an Olfactory Route to Brain Infection","volume":"27","author":"Butowt","year":"2021","journal-title":"Neuroscientist"},{"key":"10.1016\/j.bbi.2022.12.017_b0020","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1002\/cne.21087","article-title":"Expression of prokineticins and their receptors in the adult mouse brain","volume":"498","author":"Cheng","year":"2006","journal-title":"J. Comp. Neurol."},{"key":"10.1016\/j.bbi.2022.12.017_b0025","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S0197-0186(01)00094-8","article-title":"Substance P and calcitonin gene-related peptide increase IL-1\u03b2, IL-6 and TNF\u03b1 secretion from human peripheral blood mononuclear cells","volume":"40","author":"Cuesta","year":"2002","journal-title":"Neurochem. Int."},{"issue":"2","key":"10.1016\/j.bbi.2022.12.017_b0030","doi-asserted-by":"crossref","first-page":"154","DOI":"10.3390\/brainsci12020154","article-title":"Olfactory Dysfunction, Headache, and Mental Clouding in Adults with Long-COVID-19: What Is the Link between Cognition and Olfaction? A Cross-Sectional Study","volume":"12","author":"Di Stadio","year":"2022","journal-title":"Brain Sci."},{"issue":"9","key":"10.1016\/j.bbi.2022.12.017_b0035","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1080\/13543784.2022.2113054","article-title":"Investigational drugs for the treatment of olfactory dysfunction","volume":"31","author":"Di Stadio","year":"2022","journal-title":"Expert Opin. Invest. Drugs"},{"key":"10.1016\/j.bbi.2022.12.017_b0040","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/j.molmed.2022.06.005","article-title":"Olfactory dysfunction in COVID-19: pathology and long-term implications for brain health","volume":"28","author":"Doty","year":"2022","journal-title":"Trends Mol. Med."},{"key":"10.1016\/j.bbi.2022.12.017_b0045","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1002\/hbm.25741","article-title":"Olfactory loss and brain connectivity after COVID-19","volume":"43","author":"Esposito","year":"2022","journal-title":"Hum. Brain Mapp."},{"key":"10.1016\/j.bbi.2022.12.017_b0050","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/cne.10143","article-title":"Trigeminal collaterals in the nasal epithelium and olfactory bulb: A potential route for direct modulation of olfactory information by trigeminal stimuli","volume":"444","author":"Finger","year":"2002","journal-title":"J. Comp. Neurol."},{"key":"10.1016\/j.bbi.2022.12.017_b0055","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/nn.3074","article-title":"Mitochondrial Ca(2+) mobilization is a key element in olfactory signaling","volume":"15","author":"Fluegge","year":"2012","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.bbi.2022.12.017_b0060","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ncomms12932","article-title":"Prokineticin-2 upregulation during neuronal injury mediates a compensatory protective response against dopaminergic neuronal degeneration","volume":"7","author":"Gordon","year":"2016","journal-title":"Nat. Commun."},{"key":"10.1016\/j.bbi.2022.12.017_b0065","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1007\/s000110050625","article-title":"Substance P induced histamine release from nasal mucosa of subjects with and without allergic rhinitis","volume":"49","author":"Hanf","year":"2000","journal-title":"Inflamm. Res."},{"issue":"11","key":"10.1016\/j.bbi.2022.12.017_b0070","doi-asserted-by":"crossref","first-page":"5445","DOI":"10.1007\/s00405-022-07431-6","article-title":"Prevalence of acute olfactory dysfunction differs between variants of SARS-CoV-2\u2014results from chemosensitive testing in wild type, VOC alpha (B.1.1.7) and VOC delta (B.1617.2)","volume":"279","author":"Hintschich","year":"2022","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"10.1016\/j.bbi.2022.12.017_b0075","doi-asserted-by":"crossref","unstructured":"Johnson, M.B., Young, A.D., Marriott, I., Wang, H., Fernandes, A., Arturo Garc\u00eda-Horsman, J., Hughes, Z., 2017. The Therapeutic Potential of Targeting Substance P\/NK-1R Interactions in Inflammatory CNS Disorders. https:\/\/doi.org\/10.3389\/fncel.2016.00296.","DOI":"10.3389\/fncel.2016.00296"},{"issue":"2","key":"10.1016\/j.bbi.2022.12.017_b0080","doi-asserted-by":"crossref","first-page":"172","DOI":"10.3390\/life12020172","article-title":"Prokineticin-Receptor Network: Mechanisms of Regulation","volume":"12","author":"Lattanzi","year":"2022","journal-title":"Life"},{"key":"10.1016\/j.bbi.2022.12.017_b0085","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.npep.2018.06.005","article-title":"PK2\u03b2 ligand, a splice variant of prokineticin 2, is able to modulate and drive signaling through PKR1 receptor","volume":"71","author":"Lattanzi","year":"2018","journal-title":"Neuropeptides"},{"issue":"11","key":"10.1016\/j.bbi.2022.12.017_b0090","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.3390\/cells8111430","article-title":"Involvement of the Chemokine Prokineticin-2 (PROK2) in Alzheimer\u2019s Disease: From Animal Models to the Human Pathology","volume":"8","author":"Lattanzi","year":"2019","journal-title":"Cells"},{"key":"10.1016\/j.bbi.2022.12.017_b0095","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2021.640441","article-title":"The Role of Prokineticin 2 in Oxidative Stress and in Neuropathological Processes","author":"Lattanzi","year":"2021","journal-title":"Front. Pharmacol."},{"issue":"1","key":"10.1016\/j.bbi.2022.12.017_b0100","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.semcdb.2012.09.001","article-title":"Peripheral modulation of smell: Fact or fiction?","volume":"24","author":"Lucero","year":"2013","journal-title":"Seminars Cell Develop. Biol."},{"issue":"11","key":"10.1016\/j.bbi.2022.12.017_b0105","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.2174\/1570159X20666220411084612","article-title":"Potential Clinical Role of Prokineticin 2 (PK2) in Neurodegenerative Diseases","volume":"20","author":"Maftei","year":"2022","journal-title":"Curr. Neuropharmacol."},{"key":"10.1016\/j.bbi.2022.12.017_b0110","doi-asserted-by":"crossref","first-page":"4249","DOI":"10.1007\/s00018-016-2293-z","article-title":"Neuropeptide substance P and the immune response","volume":"73","author":"Mashaghi","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.bbi.2022.12.017_b0115","doi-asserted-by":"crossref","first-page":"112159","DOI":"10.1016\/j.biopha.2021.112159","article-title":"Neurokinin-1 Receptor as a potential drug target for COVID-19 treatment","volume":"143","author":"Mehboob","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.bbi.2022.12.017_b0120","doi-asserted-by":"crossref","unstructured":"Mehboob, R., Ahmad, F.J., Qayyum, A., Rana, M.A., Gilani, S.A., Tariq, M.A., Akram, J., 2020. Aprepitant as a combinant with Dexamethasone reduces the inflammation via Neurokinin 1 Receptor Antagonism in severe to critical Covid-19 patients and potentiates respiratory recovery: A novel therapeutic approach. medRxiv 2020.08.01.20166678. https:\/\/doi.org\/10.1101\/2020.08.01.20166678.","DOI":"10.1101\/2020.08.01.20166678"},{"key":"10.1016\/j.bbi.2022.12.017_b0125","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1002\/glia.23467","article-title":"Prokineticin-2 promotes chemotaxis and alternative A2 reactivity of astrocytes","volume":"66","author":"Neal","year":"2018","journal-title":"Glia"},{"key":"10.1016\/j.bbi.2022.12.017_b0130","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1152\/physrev.00012.2017","article-title":"The prokineticins: Neuromodulators and mediators of inflammation and myeloid cell-dependent angiogenesis","volume":"98","author":"Negri","year":"2018","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.bbi.2022.12.017_b0135","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1126\/science.1112103","article-title":"Dependence of Olfactory Bulb Neurogenesis on Prokineticin 2 Signaling","volume":"308","author":"Ng","year":"2005","journal-title":"Science (80-)"},{"issue":"4","key":"10.1016\/j.bbi.2022.12.017_b0140","doi-asserted-by":"crossref","first-page":"336","DOI":"10.3390\/ph14040336","article-title":"Ultramicronized Palmitoylethanolamide (um-PEA): A New Possible Adjuvant Treatment in COVID-19 patients","volume":"14","author":"Noce","year":"2021","journal-title":"Pharmaceuticals (Basel)"},{"key":"10.1016\/j.bbi.2022.12.017_b0145","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/0006-8993(87)91133-4","article-title":"Substance P depresses neuronal activity in the rat olfactory bulb in vitro and in vivo: possible mediation via gamma-aminobutyric acid release","volume":"412","author":"Olpe","year":"1987","journal-title":"Brain Res."},{"key":"10.1016\/j.bbi.2022.12.017_b0150","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1056\/NEJMoa1315200","article-title":"A Test for Creutzfeldt-Jakob Disease Using Nasal Brushings","volume":"371","author":"Orr\u00fa","year":"2014","journal-title":"N. Engl. J. Med."},{"issue":"2","key":"10.1016\/j.bbi.2022.12.017_b0155","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1007\/s00405-021-06848-9","article-title":"Smell impairment in patients with chronic rhinosinusitis: a real-life study","volume":"279","author":"Passali","year":"2022","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"10.1016\/j.bbi.2022.12.017_b0160","doi-asserted-by":"crossref","first-page":"e04646","DOI":"10.1002\/ccr3.4646","article-title":"Effectiveness of aprepitant in post-acute COVID19 syndrome","volume":"9","author":"Reinoso-Arija","year":"2021","journal-title":"Clin. Case Rep."},{"key":"10.1016\/j.bbi.2022.12.017_b0165","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.anorl.2015.08.004","article-title":"How to assess olfactory performance with the Sniffin\u2019 Sticks test\u00ae","volume":"133","author":"Rumeau","year":"2016","journal-title":"Eur. Ann. Otorhinolaryngol. Head Neck Dis."},{"issue":"4","key":"10.1016\/j.bbi.2022.12.017_b0170","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1007\/s00415-020-10131-y","article-title":"COVID-19: dealing with a potential risk factor for chronic neurological disorders","volume":"268","author":"Schirinzi","year":"2021","journal-title":"J. Neurol."},{"issue":"4","key":"10.1016\/j.bbi.2022.12.017_b0175","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1002\/mds.28458","article-title":"Increase of Prokineticin-2 in Serum of Patients with Parkinson\u2019s Disease","volume":"36","author":"Schirinzi","year":"2021","journal-title":"Mov. Disord."},{"key":"10.1016\/j.bbi.2022.12.017_b0180","doi-asserted-by":"crossref","DOI":"10.1002\/mds.28458","article-title":"Serum Substance P Is Increased in Parkinson\u2019s Disease and Correlates with Motor Impairment","author":"Schirinzi","year":"2021","journal-title":"Mov. Disord."},{"key":"10.1016\/j.bbi.2022.12.017_b0185","article-title":"Olfactory neuron Prokineticin-2 as a potential target in Parkinson\u2019s disease","author":"Schirinzi","year":"2022","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.bbi.2022.12.017_b0190","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1124\/pr.54.2.285","article-title":"The tachykinin peptide family","volume":"54","author":"Severini","year":"2002","journal-title":"Pharmacol. Rev."},{"key":"10.1016\/j.bbi.2022.12.017_b0195","doi-asserted-by":"crossref","first-page":"279","DOI":"10.4193\/Rhin17.167","article-title":"Nasal symptoms, epithelial injury and neurogenic inflammation in elite swimmers","volume":"56","author":"Steelant","year":"2018","journal-title":"Rhinology"},{"key":"10.1016\/j.bbi.2022.12.017_b0200","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1093\/brain\/awab005","article-title":"Alpha-synuclein seeds in olfactory mucosa of patients with isolated REM sleep behaviour disorder","volume":"144","author":"Stefani","year":"2021","journal-title":"Brain"},{"key":"10.1016\/j.bbi.2022.12.017_b0205","article-title":"Prognosis and persistence of smell and taste dysfunction in patients with covid-19: meta-analysis with parametric cure modelling of recovery curves","volume":"378","author":"Tan","year":"2022","journal-title":"BMJ"},{"key":"10.1016\/j.bbi.2022.12.017_b0210","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/j.dld.2013.05.010","article-title":"Genetic variants of membrane metallopeptidase genes in inflammatory bowel diseases","volume":"45","author":"Tavano","year":"2013","journal-title":"Dig. Liver Dis."},{"key":"10.1016\/j.bbi.2022.12.017_b0215","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.neubiorev.2021.10.008","article-title":"What substance P might tell us about the prognosis and mechanism of Parkinson\u2019s disease?","volume":"131","author":"Tirassa","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"10.1016\/j.bbi.2022.12.017_b0220","article-title":"Substance P\/ Neurokinin-1 Receptor, Trigeminal Ganglion, Latency, and Coronavirus Infection-Is There Any Link?","volume":"8","author":"Ullah","year":"2021","journal-title":"Front. Med."},{"issue":"0","key":"10.1016\/j.bbi.2022.12.017_b0225","article-title":"Prevalence of olfactory dysfunction in D614G, alpha, delta and omicron waves: a psychophysical case-control study","volume":"0","author":"Vaira","year":"2022","journal-title":"Rhinology"},{"key":"10.1016\/j.bbi.2022.12.017_b0230","doi-asserted-by":"crossref","first-page":"12490","DOI":"10.1523\/JNEUROSCI.2238-14.2014","article-title":"Substance P exacerbates dopaminergic neurodegeneration through neurokinin-1 receptor-independent activation of microglial NADPH oxidase","volume":"34","author":"Wang","year":"2014","journal-title":"J. Neurosci."},{"key":"10.1016\/j.bbi.2022.12.017_b0235","doi-asserted-by":"crossref","first-page":"2931","DOI":"10.1002\/cne.24719","article-title":"The PROK2\/PROKR2 signaling pathway is required for the migration of most olfactory bulb interneurons","volume":"527","author":"Wen","year":"2019","journal-title":"J. Comp. Neurol."}],"container-title":["Brain, Behavior, and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0889159122004755?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0889159122004755?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:23:28Z","timestamp":1760171008000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0889159122004755"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2]]},"references-count":47,"alternative-id":["S0889159122004755"],"URL":"https:\/\/doi.org\/10.1016\/j.bbi.2022.12.017","relation":{},"ISSN":["0889-1591"],"issn-type":[{"value":"0889-1591","type":"print"}],"subject":[],"published":{"date-parts":[[2023,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Substance P and Prokineticin-2 are overexpressed in olfactory neurons and play differential roles in persons with persistent post-COVID-19 olfactory dysfunction","name":"articletitle","label":"Article Title"},{"value":"Brain, Behavior, and Immunity","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bbi.2022.12.017","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}