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Interplay between the Endogenous Opioid System and Proteasome Complex: Beyond Signaling.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2019 Mar 21; Vol. 20 (6). Date of Electronic Publication: 2019 Mar 21. - Publication Year :
- 2019
-
Abstract
- Intracellular signaling mechanisms underlying the opioid system regulation of nociception, neurotransmitters release, stress responses, depression, and the modulation of reward circuitry have been investigated from different points of view. The presence of the ubiquitin proteasome system (UPS) in the synaptic terminations suggest a potential role of ubiquitin-dependent mechanisms in the control of the membrane occupancy by G protein-coupled receptors (GPCRs), including those belonging to the opioid family. In this review, we focused our attention on the role played by the ubiquitination processes and by UPS in the modulation of opioid receptor signaling and in pathological conditions involving the endogenous opioid system. The collective evidence here reported highlights the potential usefulness of proteasome inhibitors in neuropathic pain, addictive behavior, and analgesia since these molecules can reduce pain behavioral signs, heroin self-administration, and the development of morphine analgesic tolerance. Moreover, the complex mechanisms involved in the effects induced by opioid agonists binding to their receptors include the ubiquitination process as a post-translational modification which plays a relevant role in receptor trafficking and degradation. Hence, UPS modulation may offer novel opportunities to control the balance between therapeutic versus adverse effects evoked by opioid receptor activation, thus, representing a promising druggable target.
- Subjects :
- Animals
Humans
Neuralgia etiology
Neuralgia metabolism
Opioid-Related Disorders etiology
Opioid-Related Disorders metabolism
Protein Binding
Signal Transduction
Ubiquitin metabolism
Ubiquitination
Analgesics, Opioid metabolism
Proteasome Endopeptidase Complex metabolism
Receptors, Opioid metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 20
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 30901925
- Full Text :
- https://doi.org/10.3390/ijms20061441