Unlocking the secrets of LRRK2 function with selective kinase inhibitors

Abstract

Leucine rich repeat kinase 2 is currently considered a potential therapeutic target for the treatment of Parkinson’s disease. A number of pathological mutations, all of which lie in the dual catalytic domains of LRRK2, segregate with Parkinson’s disease in an autosomal dominant fashion. The most common mutation, G2019S, results in an increase in the kinase activity of LRRK2 and much work has therefore gone into the development of potent and specific inhibitors of LRRK2 kinase activity. A number of LRRK2 kinase inhibitors have now been employed in the search for the physiological function of LRRK2 and the targets of LRRK2 kinase activity.