Study Rationale: Chronic exposure to environmental contaminants is believed to play an important role in the initiation of Parkinson’s disease (PD). With an estimated 40,000 to 60,000 chemicals that could potentially increase the risk of PD, there is a need to develop diverse models for the large-scale investigation of PD-associated environmental exposures. Once these molecules enter the bloodstream, they may affect blood vessels prior to reaching neurons. We will therefore develop models to evaluate whether environmental toxins alter blood vessels and disrupt the blood-brain barrier that normally protects the brain.
Hypothesis: We hypothesize that a microfluidic model of the blood-brain barrier can serve as a platform for investigating the contributions of environmental factors to barrier weakening and, ultimately, neurodegeneration.
Study Design: To examine the effects of environmental toxins on blood vessels, we will produce three-dimensional brain chips using stem cells from healthy controls or from people with the SNCA triplication mutation (a mutation linked to PD). The brain chips will be treated with a selection of chemical compounds or physiological molecules associated with PD or shown to increase PD risk.
Impact on Diagnosis/Treatment of Parkinson’s disease: Successful completion of this work will shed light on the central question of environmental exposures and gene-environment interactions. It will evaluate the contributions of the blood-brain barrier to disease initiation an, in doing so, could point toward new drug targets for slowing or halting disease progression.
Next Steps for Development: We anticipate that the brain chip model could complement screening platforms focused on neurons to enhance data collection and help generate a comprehensive map of molecular initiating events that trigger PD.