Characterizing upstream regulators of glucosylceramide metabolism for Parkinson's disease and Lewy Body Dementia

Parkinson’s disease (PD) and Lewy Body Dementia (LBD) incidence is high among the aged population and mutations in the GBA gene represent one of the most common genetic risk factors for PD and LBD. Mutations in GBA leading to PD and LBD lead to a reduction in GCase activity, and GCase activity is also significantly decreased in the substantia nigra and anterior cingulate cortex in sporadic PD and LBD cases, suggesting a critical role for GCase activity in the pathophysiology of PD and LBD. Identifying upstream regulators of GBA to control glucosylceramide metabolism may suppress PD and LBD in patients with mutations in GBA or have reduced GCase activity.