Study Rationale: Many studies have shown that a protein called alpha-synuclein is abnormal in Parkinson's disease (PD), forming toxic aggregates that move through the brain and cause neuronal cell death. However, we don't understand why and how this protein becomes abnormal.
Hypothesis: We hypothesize that specific stresses experienced by the human body can change the chemistry of alpha-synuclein protein to render it toxic.
Study Design: To identify the chemical changes associated with toxic forms of alpha-synuclein, we propose engineering a “FLEXISyn platform” to isolate, quantify and identify the most toxic alpha-synuclein species and their molecular modifications. The FLEXI platform, designed by the Steen Lab, is currently unparalleled with respect to the depth and detail with which it can map and quantify molecular changes for any protein. The method is unbiased and does not rely on any previous study.
Impact on Diagnosis/Treatment of Parkinson’s Disease: The FLEXI platform previously provided unprecedented molecular and mechanistic information that has enabled the design of drugs and discovery of biomarkers for Alzheimer’s disease.
Next Steps for Development: The absolute quantitative information provided by FLEXISyn will identify the critical toxic changes in alpha-synuclein and allow dosing of patients at each stage of the disease. This information will be used to develop novel therapeutics and discover new biomarkers for PD.