The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson's disease

Recent evidence suggests that mutations inLRRK2are linked to Parkinson's disease. In this Progress article, Mark Cookson discusses how these mutations might affect LRRK2 function and its interactions with other proteins that have been implicated in Parkinson's disease, specifically α-synuclein and tau. Parkinson's disease, like many common age-related conditions, is now recognized to have a substantial genetic component. Here, I discuss how mutations in a large complex gene — leucine-rich repeat kinase 2 (LRRK2) — affect protein function, and I review recent evidence that LRRK2 mutations affect pathways that involve other proteins that have been implicated in Parkinson's disease, specifically α-synuclein and tau. These concepts can be used to understand disease processes and to develop therapeutic opportunities for the treatment of Parkinson's disease.