Research Project Description
Parkinson’s disease (PD) is a chronic, progressively debilitating neurodegenerative disease with no available cure or disease-modifying treatment at present, which can be largely attributed to the lack of biomarkers to enable early detection, diagnosis, prognosis, and stratification of PD. Leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GCase), two PD-associated proteins highly expressed in peripheral blood cells, have been identified as potential biomarkers and therapeutic targets for PD, and will be the primary focus of my project.
Objectives & Methods:
Outcomes from the above objectives will provide new information on the interaction between LRRK2 and GCase activities in peripheral blood cells and uncover how PD-associated mutations in these genes alter their activities. Results from this study will reveal any differences in LRRK2 and GCase enzymatic activity, inflammation, and lysosome function between the different cohorts (LRRK2/GBA mutation PD patients, non-manifesting mutation carriers, and idiopathic PD patients). Outcomes from objective 4 may identify peripheral blood biomarkers indicative of iRBD conversion to synucleinopathic disease, which would enable early therapeutic intervention in these patients.
Experiments will predominantly utilise flow cytometry to measure LRRK2 and GCase enzyme activity in primary blood cells obtained from patients. Other methods to be used include western blotting to determine protein levels, and cytokine ELISA assays to examine inflammatory responses.
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