Opioid system in L-DOPA-induced dyskinesia

Pan, Jing; Cai, Huaibin

doi:10.1186/s40035-017-0071-y

Cited by 41 publications

(38 citation statements)

References 56 publications

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“…In such a case, it is possible that the unopposed action of endogenous opioids following FD song would further inhibit striatal neurons. Interestingly, blocking opioid receptors in the basal ganglia have been shown to alleviate the symptoms of Levodopa-induced dyskinesia (LID; Pan and Cai, 2017). These findings are thought to result from lowering the aberrant activity of MSNs which express both μ-ORs and DA receptors (Ryan et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Altering Opioid Neuromodulation in the Songbird Basal Ganglia Modulates Vocalizations

et al. 2019

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Although the interplay between endogenous opioids and dopamine (DA) in the basal ganglia (BG) is known to underlie diverse motor functions, few studies exist on their role in modulating speech and vocalization. Vocal impairment is a common symptom of Parkinson’s disease (PD), wherein DA depletion affects striosomes rich in μ-opioid receptors (μ-ORs). Symptoms of opioid addiction also include deficiencies in verbal functions and speech. To understand the interplay between the opioid system and BG in vocalization, we used adult male songbirds wherein high levels of μ-ORs are expressed in Area X, a BG region which is part of a circuit similar to the mammalian thalamocortical-basal ganglia loop. Changes in DA, glutamate and GABA levels were analyzed during the infusion of different doses of the μ-OR antagonist naloxone (50 and 100 ng/ml) specifically in Area X. Blocking μ-ORs in Area X with 100 ng/ml naloxone led to increased levels of DA in this region without altering the number of songs directed toward females (FD). Interestingly, this manipulation also led to changes in the spectro-temporal properties of FD songs, suggesting that altered opioid modulation in the thalamocortical-basal ganglia circuit can affect vocalization. Our study suggests that songbirds are excellent model systems to explore how the interplay between μ-ORs and DA modulation in the BG affects speech/vocalization.

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Section: Discussionmentioning

confidence: 99%

Altering Opioid Neuromodulation in the Songbird Basal Ganglia Modulates Vocalizations

et al. 2019

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“… L-DOPA Dopamine agonist Increases dopamine concentrations Nausea, vomiting, low blood pressure, restlessness, drowsiness. [ 324 , 325 ] Selegiline MAO-B inhibitor Maintains L-DOPA levels Dizziness, dry mouth, insomnia, muscle pain, rash, nausea, constipation, severe headache, tachycardia, arrhythmia, hallucinations, chorea, or difficulty in breathing. [ 326 ] Creatine Boosts mitochondrial function Antioxidant, prevents MPTP-induced neuronal damage Nausea, stomach pain, diarrhea, muscle cramps; difficult breathing; swelling of face, lips, tongue, or throat, and weight gain.…”

Section: Treatment Of Pdmentioning

confidence: 99%

Current understanding of the molecular mechanisms in Parkinson's disease: Targets for potential treatments

Maiti

Manna

Dunbar

2017

Transl Neurodegener

421

305

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Gradual degeneration and loss of dopaminergic neurons in the substantia nigra, pars compacta and subsequent reduction of dopamine levels in striatum are associated with motor deficits that characterize Parkinson’s disease (PD). In addition, half of the PD patients also exhibit frontostriatal-mediated executive dysfunction, including deficits in attention, short-term working memory, speed of mental processing, and impulsivity. The most commonly used treatments for PD are only partially or transiently effective and are available or applicable to a minority of patients. Because, these therapies neither restore the lost or degenerated dopaminergic neurons, nor prevent or delay the disease progression, the need for more effective therapeutics is critical. In this review, we provide a comprehensive overview of the current understanding of the molecular signaling pathways involved in PD, particularly within the context of how genetic and environmental factors contribute to the initiation and progression of this disease. The involvement of molecular chaperones, autophagy-lysosomal pathways, and proteasome systems in PD are also highlighted. In addition, emerging therapies, including pharmacological manipulations, surgical procedures, stem cell transplantation, gene therapy, as well as complementary, supportive and rehabilitation therapies to prevent or delay the progression of this complex disease are reviewed.

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“…Primary regulators of the protein homeostasis system are molecular chaperones, which constitute a family of structurally and functionally diverse proteins with varying mechanisms of action based on cell-specific expression [ 163 ]. According to a recent mapping, the human chaperome consists of 332 genes, of which 88 are molecular chaperones and 244 are co-chaperones [ 164 ].…”

Section: Targeting Misfolded Protein Oligomers By Potentiating Thementioning

confidence: 99%

Therapeutic Strategies to Reduce the Toxicity of Misfolded Protein Oligomers

Kreiser

Wright

Block

et al. 2020

IJMS

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The aberrant aggregation of proteins is implicated in the onset and pathogenesis of a wide range of neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases. Mounting evidence indicates that misfolded protein oligomers produced as intermediates in the aggregation process are potent neurotoxic agents in these diseases. Because of the transient and heterogeneous nature of these elusive aggregates, however, it has proven challenging to develop therapeutics that can effectively target them. Here, we review approaches aimed at reducing oligomer toxicity, including (1) modulating the oligomer populations (e.g., by altering the kinetics of aggregation by inhibiting, enhancing, or redirecting the process), (2) modulating the oligomer properties (e.g., through the size–hydrophobicity–toxicity relationship), (3) modulating the oligomer interactions (e.g., by protecting cell membranes by displacing oligomers), and (4) reducing oligomer toxicity by potentiating the protein homeostasis system. We analyze examples of these complementary approaches, which may lead to the development of compounds capable of preventing or treating neurodegenerative disorders associated with protein aggregation.

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Opioid system in L-DOPA-induced dyskinesia

Cited by 41 publications

References 56 publications

Altering Opioid Neuromodulation in the Songbird Basal Ganglia Modulates Vocalizations

Altering Opioid Neuromodulation in the Songbird Basal Ganglia Modulates Vocalizations

Current understanding of the molecular mechanisms in Parkinson's disease: Targets for potential treatments

Therapeutic Strategies to Reduce the Toxicity of Misfolded Protein Oligomers

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