Managing Parkinson’s disease: moving ON with NOP.

Daniela Mercatelli, Erwan Bezard, Roberto Eleopra, Nurulain T. Zaveri, Michele Morari
Br J Pharmacol. 2020-01-01; 177(1): 28-47
DOI: 10.1111/bph.14893

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1. Br J Pharmacol. 2020 Jan;177(1):28-47. doi: 10.1111/bph.14893. Epub 2020 Jan 3.

Managing Parkinson’s disease: moving ON with NOP.

Mercatelli D(1), Bezard E(2)(3), Eleopra R(4), Zaveri NT(5), Morari M(1).

Author information:
(1)Department of Medical Sciences, Section of Pharmacology, University of Ferrara
and National Institute of Neuroscience, Ferrara, Italy.
(2)Institut des Maladies Neurodégénératives, UMR 5293, Université de Bordeaux,
Bordeaux, France.
(3)Institut des Maladies Neurodégénératives, Centre National de la Recherche
Scientifique, UMR 5293, Bordeaux, France.
(4)Neurology Unit 1, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan,
(5)Astraea Therapeutics, Medicinal Chemistry Division, Mountain View, California,

The opioid-like neuropeptide nociceptin/orphanin FQ (N/OFQ) and its receptor (NOP
receptor) contribute to Parkinson’s disease (PD) and motor complications
associated with levodopa therapy. The N/OFQ-NOP receptor system is expressed in
cortical and subcortical motor areas and, notably, in dopaminergic neurons of the
substantia nigra compacta. Dopamine depletion, as in rodent models of PD results
in up-regulation of N/OFQ transmission in the substantia nigra and
down-regulation of N/OFQ transmission in the striatum. Consistent with this, NOP
receptor antagonists relieve motor deficits in PD models by reinstating the
physiological balance between excitatory and inhibitory inputs impinging on
nigro-thalamic GABAergic neurons. NOP receptor antagonists also counteract the
degeneration of nigrostriatal dopaminergic neurons, possibly by attenuating the
excitotoxicity or modulating the immune response. Conversely, NOP receptor
agonists attenuate levodopa-induced dyskinesia by attenuating the hyperactivation
of striatal D1 receptor signalling in neurons of the direct striatonigral
pathway. The N/OFQ-NOP receptor system might represent a novel target in the
therapy of PD.

© 2019 The British Pharmacological Society.

DOI: 10.1111/bph.14893
PMCID: PMC6976791 [Available on 2021-01-01]
PMID: 31648371

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