Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jan;93(1):196-204.
doi: 10.1002/ana.26526. Epub 2022 Oct 26.

Olfactory Neuron Prokineticin-2 as a Potential Target in Parkinson's Disease

Tommaso Schirinzi  1 , Daniela Maftei  2 , Francesco M Passali  3 , Piergiorgio Grillo  1 , Henri Zenuni  1 , Davide Mascioli  1 , Riccardo Maurizi  3 , Laura Loccisano  3 , Martina Vincenzi  2 , Anna Maria Rinaldi  4 , Massimo Ralli  5 , Stefano Di Girolamo  3 , Alessandro Stefani  1 , Roberta Lattanzi  2 , Cinzia Severini  6 , Nicola B Mercuri  1   7
Affiliations

Olfactory Neuron Prokineticin-2 as a Potential Target in Parkinson's Disease

Tommaso Schirinzi et al. Ann Neurol. 2023 Jan.

Abstract

Objective: The objective of this study was to outline the dynamics of prokineticin-2 pathway in relation to clinical-pathological features of Parkinson's disease by examining olfactory neurons of patients.

Methods: Thirty-eight patients (26 de novo, newly diagnosed) and 31 sex/age-matched healthy controls underwent noninvasive mucosa brushing for olfactory neurons collection, and standard clinical assessment. Gene expression levels of prokineticin-2, prokineticin-2 receptors type 1 and 2, and prokineticin-2-long peptide were measured in olfactory neurons by real-time polymerase chain reaction (PCR); moreover, the prokineticin-2 protein and α-synuclein species (total and oligomeric) were quantified by immunofluorescence staining.

Results: Prokineticin-2 expression was significantly increased in Parkinson's disease. De novo patients had higher prokineticin-2 levels, directly correlated with Movement Disorder Society-Sponsored Revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS) part III motor score. In addition, oligomeric α-synuclein was higher in Parkinson's disease and directly correlated with prokineticin-2 protein levels. Total α-synuclein did not differ between patients and controls.

Interpretation: Prokineticin-2 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-2 pathway is activated in patients with Parkinson's disease. Specifically, prokineticin-2 expression in olfactory neurons was higher at early disease stages, proportional to motor severity, and associated with oligomeric α-synuclein accumulation. These data, consistently with preclinical findings, support prokineticin-2 as a candidate target in Parkinson's disease, and validate reliability of olfactory neurons to reflect pathological changes of the disease. ANN NEUROL 2023;93:196-204.

PubMed Disclaimer

References

    1. Petrillo S, Schirinzi T, Di Lazzaro G, et al. Systemic activation of Nrf2 pathway in Parkinson's disease. Mov Disord 2020;35:180-184. https://doi.org/10.1002/mds.27878.
    1. Schirinzi T, Sancesario GM, Di Lazzaro G, et al. CSF α-synuclein inversely correlates with non-motor symptoms in a cohort of PD patients. Parkinsonism Relat Disord 2018;61:203-206.
    1. Lang AE, Espay AJ. Disease modification in Parkinson's disease: current approaches, challenges, and future considerations. Mov Disord 2018;33:660-677.
    1. Espay AJ. Movement disorders research in 2021: cracking the paradigm. Lancet Neurol 2022;21:10-11.
    1. Krashia P, Cordella A, Nobili A, et al. Blunting neuroinflammation with resolvin D1 prevents early pathology in a rat model of Parkinson's disease. Nat Commun 2019;10:3945.

Publication types