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Managing Parkinson's disease: moving ON with NOP
Author(s) -
Mercatelli Daniela,
Bezard Erwan,
Eleopra Roberto,
Zaveri Nurulain T.,
Morari Michele
Publication year - 2020
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.14893
Subject(s) - nop , nociceptin receptor , substantia nigra , dopaminergic , pars compacta , neuroscience , opioid receptor , dopamine , striatum , chemistry , medicine , receptor , biology , agonist , opioid , opioid peptide
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 D 1 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.