Mifunctional Cembranoids for Therapy of Parkinsonís Disease
Rapid Response Innovation Awards, 2012
Although considerable achievements have been made in the understanding of pathophysiology of Parkinsonís disease (PD), there are still limited effective approaches available for PD treatment. Thus, there are strong needs for exploring new therapeutics and approaches for PD patients. The objectives of this project are to characterize therapeutic effect of beta-cembrane, a tobacco cembranoids extract, and to understand its underlying mechanisms in the treatment of Parkinsonís disease.
The therapeutic strategy proposed in this application is to use a multifunctional compound, beta-cembrane, to treat 6-hydroxydopamine (6-OHDA)-induced PD in a pre-clinical model. The models will be treated with various doses of beta-cembrane (6mg/kg, 12mg/kg) and an equal volume of vehicles or saline by intraperitoneal injection. The treatment will start at one hour after toxin injection into the brain every two days over the following three weeks. The outcome of PD in the model will be evaluated by the rotation testing and forelimb placing testing. The level of related biomarkers like VCAM-1, ICAM-1, p-Akt, ROS, dopamine, degenerating neurons and infiltration of inflammatory cells will also be detected in different brain areas.
Relevance to Diagnosis/Treatment of Parkinsonís disease:
This study is expected to provide a novel effective therapy for PD and will guide our future studies of using beta-cembrane to treat PD in humans. The success of the project will have immediate impact on therapy of Parkinsonís disease, and explore novel use of tobacco for medical purpose.
Upon completion of this project, we expect that beta-cembrane will have a therapeutic effect on a PD pre-clinical model. Beta-cembrane significantly protects the model against 6-OHDA-induced symptoms of Parkinsonís disease, and the loss of dopaminergic neurons and inflammation.
Beta-cembrane (4R) is one extract from tobacco plants, and it has been found that 4R has a protective effect on neurons against some damage. Here, we have found that 4R also had therapeutic effects on a Parkinsonís disease model. 4R at doses of 6mg/kg, 12mg/kg improved 6-OHDA-induced symptoms and protected neurons from death in a PD model. The possible mechanisms of 4R protection are promoting protective protein activity and inhibiting damaging protein functions in neurons, as well as suppressing inflammation in the brain. More studies will be needed to elucidate the mechanism underling 4R protection in Parkinsonís disease. This project may provide a new lead compound for the development of novel therapeutic agents for Parkinsonís disease.† ††
Location: Cincinnati, Ohio