The Prokineticin system is downregulated in idiopathic rapid eye movement sleep behavior disorder: evidence from olfactory neurons
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Le résumé fourni par la source
STUDY OBJECTIVES: PROK2 is a peptide expressed in the adult brain mediating neuroprotective functions. Previous studies reported an upregulation of prokineticin system in Parkinson's disease (PD), but evidence in prodromal α-synucleinopathies was lacking. We investigated the expression of prokineticin-2 (PROK2) and its receptors (PKR1 and PKR2), along with oligomeric α-synuclein (oligo α-syn) as a marker of α-synuclein pathology, in olfactory neurons (ONs) from individuals with idiopathic rapid eye movement sleep behavior disorder (iRBD). METHODS: Olfactory neurons, obtained by nasal brush from 28 idiopathic rapid eye movement sleep behavior disorder subjects (age: 71.2 ± 7.4 years; males: 89.3%; duration: 4.9 ± 2.5 years) and 28 healthy controls (HCs) (age:67.2 ± 11.5 years; 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. RESULTS: In the idiopathic rapid eye movement sleep behavior disorder group, prokineticin-2 protein expression was reduced in both ONs (immunofluorescence: F(1,26) = 15.289, p < .001; western blot: F(1,12) = 9.073, p = .011) and serum compared with HCs (western blot: F(1,12) = 4.557, 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) = 16.131, p < .001; real-time polymerase-chain-reaction for prokineticin receptor-2: F(1,39) = 4.946, p = .032). Oligo α-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) = 3.169, p = .092). CONCLUSIONS: In contrast with findings in Parkinson's 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 α-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.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- The Prokineticin system is downregulated in idiopathic rapid eye movement sleep behavior disorder: evidence from olfactory neurons
- Date Crossref
- 14/01/2026
- Éditeur
- Oxford University Press (OUP)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
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University of Pavia Department of Brain and Behavioral Sciences pays non établi dans la noticeUniversité ou école supérieure
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NYU Langone Health pays non établi dans la noticeÉtablissement de santé
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Sapienza University of Rome Department of Physiology and Pharmacology “V. Erspamer” pays non établi dans la noticeUniversité ou école supérieure
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University of Rome Tor Vergata pays non établi dans la noticeUniversité ou école supérieure
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Policlinico Tor Vergata pays non établi dans la noticeÉtablissement de santé
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Policlinico San Matteo Fondazione pays non établi dans la noticeÉtablissement de santé
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IRCCS Mondino Foundation pays non établi dans la noticeOrganisation à but non lucratif
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The Marlene and Paolo Fresco Institute for Parkinson’s and Movement Disorders pays non établi dans la noticeStructure de recherche
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Tor Vergata University of Rome Unit of Neurology pays non établi dans la noticeUniversité ou école supérieure
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Department of Brain and Behavioral Sciences — University of Pavia, NYU Langone Health et Department of Physiology and Pharmacology “V. Erspamer” — Sapienza University of Rome, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.