Biomedical Research Foundation Academy Of AthensAcademy Of Athens
Research Highlights :Nurr1:RXRα Heterodimer Activation as Monotherapy for Parkinson’s Disease



Demetrios Vassilatis, Investigator - Assistant Professor Level at BRFAA, recently published a paper along with his colleagues in the journal PNAS.




Brief Overview of Publication

In Parkinson’s Disease (PD) dopamine-producing-neurons gradually degenerate resulting in dopamine deficiency and in the main symptoms of PD. Current medications relieve symptoms by replenishing dopamine, but do not impede neurodegeneration and their chronic use causes serious side effects called dyskinesias. Current drug discovery efforts aim either at new symptomatic DA replacement treatments and alleviating dyskinesias, or towards stopping neurodegeneration.

Using synthetic chemistry, we designed the chemical compound BRF110 to activate the Nurr1:RXRα protein-complex which is involved in the development and function of dopamine neurons. BRF110 replenishes dopamine in PD mouse models and improves symptoms without inducing dyskinesias. Additionally, BRF110 prevents dopamine-producing-neuron loss which is caused by either PD causing toxins or PD associated mutations. Our findings indicate that dopamine production and neuroprotection are controlled by the Nurr1:RXRα protein-complex and point to a monotherapy approach for the treatment of PD.

Athanasios D. Spathis, Xenophon Asvos, Despina Ziavra, Theodoros Karampelas, Stavros Topouzis, Zoe Cournia, Xiaobing Qing, Pavlos Alexakos, Lisa M. Smits, Christina Dalla, Hardy J. Rideout, Jens Christian Schwamborn, Constantin Tamvakopoulos, Demosthenes Fokas, and Demetrios K. Vassilatis
Nurr1:RXRα heterodimer activation as monotherapy for Parkinson’s disease
PNAS 2017 ; published ahead of print March 27, 2017, doi:10.1073/pnas.1616874114