Dopamine D2 receptor TaqIA and TaqIB polymorphisms in Parkinson's disease

2003 ◽  
Vol 18 (5) ◽  
pp. 593-595 ◽  
Author(s):  
Eng-King Tan ◽  
Yanni Tan ◽  
Anthea Chai ◽  
Christopher Tan ◽  
Hui Shen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Dopamine D2

scholarly journals Revealing Adenosine A2A-Dopamine D2 Receptor Heteromers in Parkinson’s Disease Post-Mortem Brain through a New AlphaScreen-Based Assay

2019 ◽  
Vol 20 (14) ◽  
pp. 3600 ◽  
Author(s):  
Víctor Fernández-Dueñas ◽  
Maricel Gómez-Soler ◽  
Marta Valle-León ◽  
Masahiko Watanabe ◽  
Isidre Ferrer ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dynamic Range ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Post Mortem ◽  
Dopamine D2 ◽  
Post Mortem Brain ◽  
Receptor Heteromers ◽  
Adenosine A2a

Background: Several biophysical techniques have been successfully implemented to detect G protein-coupled receptors (GPCRs) heteromerization. Although these approaches have made it possible to ascertain the presence of GPCR heteromers in animal models of disease, no success has been accomplished in pathological human post-mortem brains. The AlphaScreen technology has been consistently used to quantify small analyte accumulation or depletion, bimolecular interactions, and post-translational modifications. The high signal-to-background, dynamic range and sensitivity exhibited by this technology support that it may be suitable to detect GPCR heteromers even under non-optimal conditions. Methods: Here, we describe the development of a new AlphaScreen assay to detect GPCR oligomers in human post-mortem brain. Results: Adenosine A2A-dopamine D2 receptor (A2AR/D2R) heteromer formation was monitored in caudate from healthy and Parkinson’s disease (PD) subjects. The approach was first validated using striatal membranes from wild type and A2AR deficient mice. Secondly, we took advantage of the 6-hydroxydopamine hemiparkinsonian rat model to validate previous results. In addition, finally, A2AR/D2R heteromer formation was assessed in caudate membranes from human post-mortem brains. Importantly, our preliminary results revealed an increase in A2AR/D2R heteromer formation in PD brains. Conclusions: The new AlphaScreen assay allowed assessing GPCR heteromers in human post-mortem brains with high sensitivity.

scholarly journals Dopamine D2 receptor gene variants and response to rasagiline in early Parkinson’s disease: a pharmacogenetic study

Brain ◽  
2016 ◽  
Vol 139 (7) ◽  
pp. 2050-2062 ◽  
Author(s):  
Mario Masellis ◽  
Shannon Collinson ◽  
Natalie Freeman ◽  
Maria Tampakeras ◽  
Joseph Levy ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopamine D2 Receptor ◽  
Receptor Gene ◽  
D2 Receptor ◽  
Gene Variants ◽  
Pharmacogenetic Study ◽  
Dopamine D2 ◽  
Early Parkinson’S Disease

scholarly journals Dopamine D2 Long Receptors Are Critical for Caveolae-Mediated α-Synuclein Uptake in Cultured Dopaminergic Neurons

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 49
Author(s):  
Ichiro Kawahata ◽  
Tomoki Sekimori ◽  
Haoyang Wang ◽  
Yanyan Wang ◽  
Toshikuni Sasaoka ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Dopamine Neurons ◽  
Fatty Acid Binding ◽  
Caveolin 1 ◽  
Dopamine D2 ◽  
C Terminus

α-synuclein accumulation into dopaminergic neurons is a pathological hallmark of Parkinson’s disease. We previously demonstrated that fatty acid-binding protein 3 (FABP3) is critical for α-synuclein uptake and propagation to accumulate in dopaminergic neurons. FABP3 is abundant in dopaminergic neurons and interacts with dopamine D2 receptors, specifically the long type (D2L). Here, we investigated the importance of dopamine D2L receptors in the uptake of α-synuclein monomers and their fibrils. We employed mesencephalic neurons derived from dopamine D2L−/−, dopamine D2 receptor null (D2 null), FABP3−/−, and wild type C57BL6 mice, and analyzed the uptake ability of fluorescence-conjugated α-synuclein monomers and fibrils. We found that D2L receptors are co-localized with FABP3. Immunocytochemistry revealed that TH+ D2L−/− or D2 null neurons do not take up α-synuclein monomers. The deletion of α-synuclein C-terminus completely abolished the uptake to dopamine neurons. Likewise, dynasore, a dynamin inhibitor, and caveolin-1 knockdown also abolished the uptake. D2L and FABP3 were also critical for α-synuclein fibrils uptake. D2L and accumulated α-synuclein fibrils were well co-localized. These data indicate that dopamine D2L with a caveola structure coupled with FABP3 is critical for α-synuclein uptake by dopaminergic neurons, suggesting a novel pathogenic mechanism of synucleinopathies, including Parkinson’s disease.

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