Noah Lubben, Julia K Brynildsen, Connor M Webb, Howard L Li, Cheryl E G Leyns, Lakshmi Changolkar, Bin Zhang, Emily S Meymand, Mia O'Reilly, Zach Madaj, Daniella DeWeerd, Matthew J Fell, Virginia M Y Lee, Dani S Bassett, Michael X Henderson
BACKGROUND: Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson's disease (PD). These mutations elevate the LRRK2 kinase activity, making LRRK2 kinase inhibitors an attractive therapeutic. LRRK2 kinase activity has been consistently linked to specific cell signaling pathways, mostly related to organelle trafficking and homeostasis, but its relationship to PD pathogenesis has been more difficult to define. LRRK2-PD patients consistently present with loss of dopaminergic neurons in the substantia nigra but show variable development of Lewy body or tau tangle pathology...
March 4, 2024: Translational Neurodegeneration