An in vivo pharmacological evaluation of pardoprunox (SLV308) — A novel combined dopamine D2/D3 receptor partial agonist and 5-HT1A receptor agonist with efficacy in experimental models of Parkinson's disease

2010 ◽  
Vol 20 (8) ◽  
pp. 582-593 ◽  
Author(s):  
C.A. Jones ◽  
L.C. Johnston ◽  
M.J. Jackson ◽  
L.A. Smith ◽  
G. van Scharrenburg ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Receptor Agonist ◽  
Partial Agonist ◽  
Experimental Models ◽  
D3 Receptor ◽  
Pharmacological Evaluation ◽  
Dopamine D2

scholarly journals DOPAL initiates αSynuclein-mediated impaired proteostasis in neuronal projections leading to enhanced vulnerability in Parkinson's disease.

2021 ◽  
Author(s):  
Anna Masato ◽  
Nicoletta Plotegher ◽  
Andrea Thor ◽  
Stephen Adams ◽  
Michele Sandre ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Protein Quality ◽  
Motor Impairment ◽  
Experimental Models ◽  
Early Event ◽  
In Vivo Models ◽  
Nigrostriatal Neuron ◽  
Presynaptic Protein

Dopamine dyshomeostasis has been acknowledged to be among the determinants of nigrostriatal neuron degeneration in Parkinson's disease (PD). Several studies in experimental models and postmortem PD patients underlined increasing levels of the aldehydic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is highly reactive towards proteins. DOPAL has been shown to covalently modify the presynaptic protein αSynuclein (αSyn), whose misfolding and aggregation represent a major trait of PD pathology, triggering αSyn oligomerization in dopaminergic neurons. Here, we demonstrated that DOPAL elicits αSyn neuronal accumulation and hampers αSyn clearance at synapses and the soma. By combining cellular and in vivo models, we provided evidence that DOPAL-induced αSyn buildup lessens neuronal resilience, compromises synaptic integrity, and overwhelms protein quality control pathways, specifically at neuronal projections. The resulting progressive decline of neuronal homeostasis leads to dopaminergic neuron loss and motor impairment, corroborating the αSyn-DOPAL interplay as an early event in PD neurodegeneration.

scholarly journals Dopamine D3 Receptor Ligand Suppresses the Expression of Levodopa-Induced Dyskinesia in Nonhuman Primate Model of Parkinson's Disease

2021 ◽  
Author(s):  
Thomas Oh ◽  
Elyas Daadi ◽  
Jeffrey Kim ◽  
Etienne Daadi ◽  
Peng-Jen Chen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Partial Agonist ◽  
Nigrostriatal System ◽  
Dopamine D3 Receptor ◽  
D3 Receptor ◽  
Lead Compound ◽  
Primate Model ◽  
Medical Needs ◽  
Dopamine D3

Abstract Parkinson’s disease (PD) is a complex multisystem, chronic and so far incurable disease with significant unmet medical needs. The incidence of PD increases with aging and the expected burden will continue to escalate with our aging population. Since its discovery in the 1961 levodopa remains the gold standard pharmacotherapy for PD. However, the progressive nature of the neurodegenerative process in and beyond the nigrostriatal system causes a multitude of side effects, including levodopa-induced dyskinesia within 5 years of therapy. Attenuating dyskinesia has been a significant challenge in the clinical management of PD. We report on a small molecule that eliminates the expression of levodopa-induced dyskinesia and significantly improves PD-like symptoms. The lead compound PD13R we discovered is a dopamine D3 receptor partial agonist with high affinity and selectivity, orally active and with desirable drug-like properties. Future studies are aimed at developing this lead compound for treating PD patients with dyskinesia.

Neuroprotective Effects of Resveratrol in In vivo and In vitro Experimental Models of Parkinson’s Disease: a Systematic Review

2022 ◽  
Author(s):  
Michele Goulart dos Santos ◽  
Lucia Emanueli Schimith ◽  
Corinne André-Miral ◽  
Ana Luiza Muccillo-Baisch ◽  
Bruno Dutra Arbo ◽  
...  
Keyword(s):  
Systematic Review ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Experimental Models ◽  
Neuroprotective Effects

scholarly journals Exercise elevates dopamine D2 receptor in a mouse model of Parkinson's disease: In vivo imaging with [18F]fallypride

2010 ◽  
Vol 25 (16) ◽  
pp. 2777-2784 ◽  
Author(s):  
Marta G. Vučcković ◽  
Quanzheng Li ◽  
Beth Fisher ◽  
Angelo Nacca ◽  
Richard M. Leahy ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
In Vivo Imaging ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Dopamine D2
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