LRRK2

1. 본문

LRRK2 (Leucine-Rich Repeat Kinase 2), also known as dardarin and PARK8, is a large, multi-domain protein kinase encoded by the *LRRK2* gene. It's a member of the leucine-rich repeat kinase family and plays a significant role in cellular processes.

Here's a breakdown of key aspects of LRRK2:
Function:

• The LRRK2 protein possesses several domains, including:
• Armadillo repeats (ARM)
• Ankyrin repeats (ANK)
• Leucine-rich repeats (LRR)
• A kinase domain
• A RAS domain
• A GTPase domain
• A WD40 domain
• These domains suggest roles in protein-protein interactions and signaling pathways.
• It exhibits both kinase activity (transferring phosphate groups) and GTPase activity.
• LRRK2 is found mainly in the cytoplasm but can also associate with the outer mitochondrial membrane.
• It is expressed in the brain and other tissues.

• Parkinson's Disease (PD): Mutations in the *LRRK2* gene are the most common genetic cause of familial autosomal dominant Parkinson's disease. These mutations can also increase risk of sporadic forms of PD.
• Over 100 *LRRK2* gene mutations have been linked to PD.
• The G2019S mutation, located in the kinase domain, is a prevalent mutation that increases kinase activity.
• The R1441C mutation is located in the ROC-COR domain and affects GTPase and kinase activity.
• Crohn's Disease: Variants of the *LRRK2* gene are also associated with an increased risk of Crohn's disease.
• It plays roles in the autophagy pathway, and lysosomal activity.

• Because pathogenic mutations in LRRK2 often lead to increased kinase activity, it is considered an attractive therapeutic target for Parkinson's disease.
• LRRK2 inhibitors have been developed.
• Research is ongoing to determine the precise mechanisms by which LRRK2 mutations contribute to disease and to develop effective therapies targeting this protein.
• Rab GTPases have recently been identified as substrates for LRRK2 kinase activity.
• LRRK2 is expressed at low levels in neurons and high levels in immune cells.