Objective/Rationale:
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been linked to Parkinson’s disease (PD). The most prevalent mutation, G2019S, results in increased LRRK2 kinase activity in vitro (laboratory experiments using an isolated part of an organism). Scientists hypothesize that increased kinase activity — either through inappropriate regulation (in sporadic disease) or mutations such as G2019S — contribute to the degeneration of neurons in PD. However, to date, there is no direct evidence of increased LRRK2 kinase activity in patient brains from either G2019S mutation carriers or patients with sporadic disease. This project measures LRRK2 levels and activity in sporadic PD brains compared to age-matched controls.
Project Description:
Researchers will use existing and new techniques, which they have developed, to measure LRRK2 levels, biochemical forms and activity in brain samples from sporadic Parkinson’s disease patients and age-matched controls. Tissue provided through collaboration with the Arizona Parkinson’s Disease Consortium are well characterized in terms of clinical and neuropathological assessments. The researchers will use biochemical techniques to determine levels and immunoprecipitation-kinase experiments to measure activity.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Scientists are developing LRRK2 kinase inhibitors as potential therapeutics, and data from this project could support that work and move these programs forward into the clinic. Such a therapy could be disease-modifying, slowing or halting PD progression.
Anticipated Outcome:
The researchers anticipate to find increased LRRK2 kinase activity in the brain tissue of Parkinson’s patients compared to that of controls.