Abstract
Parkinson’s disease (PD) is a dopaminergic-related pathology in which basal ganglia functioning are altered. It has been postulated that a direct receptor-receptor – i.e. dopamine D2 receptor (D2R) and adenosine A2A receptor (A2AR) – interaction may be finely regulating this brain area. Accordingly, elucidating whether the pathology prompts changes on these structures could grant valuable information for the design of new PD therapies. Here, we first resolved a long-standing question concerning D2R-A2AR assembly in native tissue. Thus, by means of different complementary experimental approaches (i.e. immunoelectron microscopy, proximity ligation assay and TR-FRET), we unambiguously identified native D2R/A2AR oligomers in rat striatum. Subsequently, we determined that under pathological conditions (i.e. in a rat PD model) D2R-A2AR interaction was impaired. Collectively, these results provide definitive evidence for a native D2R/A2AR oligomer alteration in experimental parkinsonism, thus conferring the rationale for appropriate oligomer-based PD treatments.
- Received September 4, 2014.
- Accepted November 10, 2014.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Article navigation
Related articles
Cited by...
More in this TOC section
Similar articles
Subject collections
Other journals from The Company of Biologists
Editor’s Choice – Altered expression of the Cdk5 activator-like protein, Cdk5α, causes neurodegeneration, in part by accelerating the rate of aging
By developing a comprehensive and quantitative metric for physiological age of Drosophila, Edward Giniger and colleagues show that a neurodegeneration mutant produces its effects in part by accelerating the absolute rate of aging.
First Person interviews
Have you seen our interviews with the early-career first authors of our papers? Recently, we caught up with first authors Sarah Foriel, Henna Myllymäki and Mirja Niskanen, Wenqing Zhou, Rifdat Aoidi and Amy Irving.
Review – Metastasis in context: modeling the tumor microenvironment with cancer-on-a-chip approaches
In a new Review article, Jaap M. J. den Toonder and colleagues evaluate the recent contributions of cancer-on-a-chip models to our understanding of the tumor microenvironment and its role in the onset of metastasis. The authors also provide an outlook for future applications of this emerging technology.
DMM Conference Travel Grants
Are you an early career scientist with plans to attend a scientific meeting, conference, workshop or course relating to the areas of research covered by DMM? The next round of applications for DMM Conference Travel Grants closes on 4 May 2018. Find out more here and get your application in soon.
Why should you publish your next paper in DMM?
DMM aims to promote human health by encouraging collaboration between basic and clinical researchers, covering a diverse range of diseases, approaches and models. Our Editors are all active researchers in the field – your peers, colleagues and mentors, who know how much work has gone into every paper. Recently, we have introduced format-free submission, and we accept peer review reports from other journals, making submission as easy as possible for our authors. Send us your next great paper – publish with us and you'll be in good company.