Promising Outcomes of Original Grant:
Since LRRK2 is a major genetic risk factor for Parkinson's disease (PD), much work has been devoted to LRRK2 function in neurons. However, LRRK2 is abundantly expressed in the immune system, offering a unique opportunity to study the pathological connections between the immune and nervous systems.
Objectives for Supplemental Investigation:
We have recently shown a cellular signaling pathway by which LRRK2 is induced by interferon-gamma (an immune system drug) in macrophages (immune cells). In tight technical exchange with our Harvard partner, we measured LRRK2 kinase activity in naïve and stimulated THP-1, a popular laboratory cell line originating from leukemia (blood cancer) research. The work will be extended to human biosamples, exploiting our extensively characterized biobank, particularly involving LRRK2 mutation holders. We will compare LRRK2 activities in aged individuals, those with sporadic (no known cause) PD and those with PD linked to LRRK2 gene mutations.
Importance of This Research for the Development of a New PD Therapy:
This study aims to establish the conditions under which LRRK2 is active in blood cells. Measurement of LRRK2 kinase activity may become a peripheral biomarker for the diagnosis and follow up of those with PD. If LRRK2 inhibitors become a treatment option, LRRK2 kinase activity measurements in blood cells will be a direct measure of therapeutic success.