Mutations in LRRK2 and PINK1 are linked to Parkinson’s disease. Loss of PINK1 doesn't affect LRRK2-mediated Rab phosphorylation. Both genes impair ciliogenesis through parallel pathways, suggesting a common therapeutic strategy for PD.
Mice with LRRK2 R1441C and PINK1 KO mutations were crossed to create double mutant lines: LRRK2 WT/PINK1 WT, LRRK2 RC/PINK1 WT, LRRK2 WT/PINK1 KO, and LRRK2 RC/PINK1 KO.
Research on LRRK2 in Parkinson's disease has advanced, revealing how mutations activate the kinase, phosphorylate Rab proteins, disrupt cell functions like Hedgehog signaling, and contribute to the disease. LRRK2 inhibitors show promise for therapy.
