Study Rationale:
Genes implicated in Parkinson's disease (PD), such as alpha-synuclein, DJ-1 and LRRK2, strongly influence the effect of environmental toxins, such as pesticide rotenone know to cause Parkinson's. Additionally, rotenone and other PD-relevant environmental toxins can activate proteins implicated in Parkinson's. In this study, we will investigate these associations to better understand common mechanisms of disease and potentially to identify new therapeutic strategies.
Hypothesis:
Investigation of the link between the genetic and environmental factors that cause PD will help identify opportunities for therapeutic intervention and new therapeutic strategies.
Study Design:
In a series of four concurrent projects, we will first assess whether activation of LRRK2 -- a strong genetic contributor to Parkinson's disease -- is a common feature of toxins that may cause the disease. Secondly, we will develop a relatively simple blood test for measuring PD. Next, we will examine changes in brain cells' use of calcium and the role of calcium in causing Parkinson's. Lastly, we will examine potential roles of dopamine in the cause and symptoms of PD.
Impact on Diagnosis/Treatment of Parkinson's disease:
We anticipate this work to produce new disease-modifying treatments for PD with an unknown cause. Additionally, if we are successful, we will develop a new biomarker -- objective measure of disease -- useful in Parkinson's diagnosis as well as clinical research.
Next Steps for Development:
Future clinical studies will test the utility of the blood-based biomarker under development.