We have found that alpha-synuclein nitration and aggregation — which may play a role in Parkinson’s disease — is catalyzed by an enzyme that we have termed synuclein nitrase. In this project, we plan to determine synuclein nitrase’s protein sequence, which will aid in our ability to develop a drug targeting alpha-synuclein nitration and aggregation and thereby Parkinson’s disease.
Because alpha-synuclein aggregation is believed to cause Parkinson’s disease, by inhibiting synuclein nitrase we may be able will slow down disease progression.
In this project, we plan to determine synuclein nitrase’s identity by following alpha-synuclein nitration activity through a purification process. The first three steps of this purification have been validated. Additional steps are being developed. Upon determination of the protein sequence, we will confirm its nitration and aggregation activity in both our biochemical assay and in neurons derived from induced pluripotent stem cells.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
This project may help characterize a drug target, which could lead to therapies that could slow Parkinson’s progression.
Next Steps for Development:
After completing this part of the project, we will develop and test a drug candidate against synuclein nitrase.