LRRK2

Leucine-rich repeat kinase 2 (LRRK2) is an enzyme that in humans is encoded by the PARK8 gene. LRRK2 is a member of the leucine-rich repeat kinase family. Variants of this gene are associated with an increased risk of Parkinson's disease (PD)and also Crohn's disease (CD). Leucine-rich repeat kinase 2 (LRRK2) is the gene responsible for autosomal-dominant PD, PARK8, which is originally defined by linkage analysis of a Japanese family. LRRK2 is a complex kinase consisting of LRR, ROC, COR, kinase, and WD40 domains. LRRK2 plays a key role in axonal extension, autophagy, proliferation, and survival of neurons. In addition to neurons, LRRK2 is highly expressed in immune cells such as B cells, macrophages, and microglia. Several studies have demonstrated that LRRK2 is related to inflammatory responses of microglia that could be involved in the development and progression of neurodegeneration. LRRK2 is a large, multidomain protein containing two catalytic domains: a Ras of complex proteins (Roc) G-domain and a kinase domain. Leucine-rich repeat kinase 2 (LRRK2) represents a promising drug target for treatment and prevention of Parkinson’s disease (PD), because mutations in LRRK2 are the most common cause of Mendelian forms of the disease. PD-associated LRRK2 variants show decreased GTPase and increased kinase activity.