{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:40:07Z","timestamp":1791430807274,"version":"4.3.3"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of University and Research (MUR), National Recovery and Resilience Plan","award":["MNESYS (PE0000006)"],"award-info":[{"award-number":["MNESYS (PE0000006)"]}]},{"name":"Ministry of University and Research (MUR), National Recovery and Resilience Plan","award":["DN. 1553 11.10.2022"],"award-info":[{"award-number":["DN. 1553 11.10.2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Study Objectives<\/jats:title>\n                    <jats:p>PROK2 is a peptide expressed in the adult brain mediating neuroprotective functions. Previous studies reported an upregulation of prokineticin system in Parkinson\u2019s disease (PD), but evidence in prodromal \u03b1-synucleinopathies was lacking. We investigated the expression of prokineticin-2 (PROK2) and its receptors (PKR1 and PKR2), along with oligomeric \u03b1-synuclein (oligo \u03b1-syn) as a marker of \u03b1-synuclein pathology, in olfactory neurons (ONs) from individuals with idiopathic rapid eye movement sleep behavior disorder (iRBD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Olfactory neurons, obtained by nasal brush from 28 idiopathic rapid eye movement sleep behavior disorder subjects (age: 71.2\u00a0\u00b1\u00a07.4\u00a0years; males: 89.3%; duration: 4.9\u00a0\u00b1\u00a02.5\u00a0years) and 28 healthy controls (HCs) (age:67.2\u00a0\u00b1\u00a011.5\u00a0years; males:64.2%), were analyzed using real-time polymerase-chain-reaction (RT-PCR), immunofluorescence (IF), and western blot (WB). In a subgroup of subjects, results were validated in serum.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the idiopathic rapid eye movement sleep behavior disorder group, prokineticin-2 protein expression was reduced in both ONs (immunofluorescence: F(1,26)\u2009=\u200915.289, p &amp;lt; .001; western blot: F(1,12)\u2009=\u20099.073, p = .011) and serum compared with HCs (western blot: F(1,12)\u2009=\u20094.557, p = .050). Idiopathic rapid eye movement sleep behavior disorder subjects showed lower mRNA expression of prokineticin receptors compared with healthy controls (real-time polymerase-chain-reaction for prokineticin receptor-1: F(1,26)\u2009=\u200916.131, p &amp;lt; .001; real-time polymerase-chain-reaction for prokineticin receptor-2: F(1,39)\u2009=\u20094.946, p = .032). Oligo \u03b1-syn accumulation in olfactory neurons was higher in idiopathic rapid eye movement sleep behavior disorder than healthy controls, yet the difference only tended to statistical significance (immunofluorescence: F(1,18)\u2009=\u20093.169, p = .092).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In contrast with findings in Parkinson\u2019s disease, we found a downregulation of prokineticin system in idiopathic rapid eye movement sleep behavior disorder. The causes of prokineticin system downregulation in this prodromal stage may be multiple. The absence of clear oligo \u03b1-syn accumulation, known trigger of prokineticin-2, may play a role. On the other hand, a lack of activation of this system might act as predisposing factor for the development of idiopathic rapid eye movement sleep behavior disorder and, subsequently, full-blown neurodegeneration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/sleep\/zsag006","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T12:21:11Z","timestamp":1768220471000},"source":"Crossref","is-referenced-by-count":3,"title":["The Prokineticin system is downregulated in idiopathic rapid eye movement sleep behavior disorder: evidence from olfactory neurons"],"prefix":"10.1093","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8196-3914","authenticated-orcid":false,"given":"Piergiorgio","family":"Grillo","sequence":"first","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia , Pavia ,","place":["Italy"]},{"name":"IRCCS Mondino Foundation , Pavia ,","place":["Italy"]},{"name":"The Marlene and Paolo Fresco Institute for Parkinson\u2019s and Movement Disorders, Department of Neurology, NYU Langone Health , New York, NY ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8679-2840","authenticated-orcid":false,"given":"Daniela","family":"Maftei","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology \u201cV. Erspamer\u201d, Sapienza University of Rome , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6224-037X","authenticated-orcid":false,"given":"Alessandra","family":"Calculli","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia , Pavia ,","place":["Italy"]},{"name":"IRCCS Mondino Foundation , Pavia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2517-6278","authenticated-orcid":false,"given":"Tommaso","family":"Schirinzi","sequence":"additional","affiliation":[{"name":"Unit of Neurology, Department of Systems Medicine, Tor Vergata University of Rome , Rome ,","place":["Italy"]},{"name":"Unit of Neurology, Fondazione PTV - Tor Vergata University Hospital , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6059-8783","authenticated-orcid":false,"given":"Simone","family":"Mauramati","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head Neck Surgery, University of Pavia, IRCCS Policlinico San Matteo Foundation , Pavia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3140-4513","authenticated-orcid":false,"given":"Martina","family":"Vincenzi","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology \u201cV. Erspamer\u201d, Sapienza University of Rome , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Di Certo","sequence":"additional","affiliation":[{"name":"National Research Council (CNR), Institute of Biochemistry and Cell Biology (IBBC) , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5536-5160","authenticated-orcid":false,"given":"Francesca","family":"Gabanella","sequence":"additional","affiliation":[{"name":"National Research Council (CNR), Institute of Biochemistry and Cell Biology (IBBC) , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8445-8535","authenticated-orcid":false,"given":"Deborah","family":"Di Martino","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia , Pavia ,","place":["Italy"]},{"name":"IRCCS Mondino Foundation , Pavia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0330-0087","authenticated-orcid":false,"given":"Marco","family":"Benazzo","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head Neck Surgery, University of Pavia, IRCCS Policlinico San Matteo Foundation , Pavia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6932-704X","authenticated-orcid":false,"given":"Cinzia","family":"Severini","sequence":"additional","affiliation":[{"name":"National Research Council (CNR), Institute of Biochemistry and Cell Biology (IBBC) , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6377-9256","authenticated-orcid":false,"given":"Roberta","family":"Lattanzi","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology \u201cV. 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