{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T16:16:11Z","timestamp":1790525771550,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T00:00:00Z","timestamp":1666742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004271","name":"Sapienza Universit\u00e0 di Roma","doi-asserted-by":"publisher","award":["Grandi Progetti 2021"],"award-info":[{"award-number":["Grandi Progetti 2021"]}],"id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The objective of this study was to outline the dynamics of prokineticin\u20102 pathway in relation to clinical\u2010pathological features of Parkinson's disease by examining olfactory neurons of patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirty\u2010eight patients (26 de novo, newly diagnosed) and 31 sex\/age\u2010matched healthy controls underwent noninvasive mucosa brushing for olfactory neurons collection, and standard clinical assessment. Gene expression levels of prokineticin\u20102, prokineticin\u20102 receptors type 1 and 2, and prokineticin\u20102\u2010long peptide were measured in olfactory neurons by real\u2010time polymerase chain reaction (PCR); moreover, the prokineticin\u20102 protein and \u03b1\u2010synuclein species (total and oligomeric) were quantified by immunofluorescence staining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Prokineticin\u20102 expression was significantly increased in Parkinson's disease. De novo patients had higher prokineticin\u20102 levels, directly correlated with Movement Disorder Society\u2010Sponsored Revision of the Unified Parkinson Disease Rating Scale (MDS\u2010UPDRS) part III motor score. In addition, oligomeric \u03b1\u2010synuclein was higher in Parkinson's disease and directly correlated with prokineticin\u20102 protein levels. Total \u03b1\u2010synuclein did not differ between patients and controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Prokineticin\u20102 is a chemokine showing neuroprotective effects in experimental models of Parkinson's disease, but translational proof of its role in patients is still lacking. Here, we used olfactory neurons as the ideal tissue to analyze molecular stages of neurodegeneration in vivo, providing unprecedented evidence that the prokineticin\u20102 pathway is activated in patients with Parkinson's disease. Specifically, prokineticin\u20102 expression in olfactory neurons was higher at early disease stages, proportional to motor severity, and associated with oligomeric \u03b1\u2010synuclein accumulation. These data, consistently with preclinical findings, support prokineticin\u20102 as a candidate target in Parkinson's disease, and validate reliability of olfactory neurons to reflect pathological changes of the disease. 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