Leucine-rich repeat kinase 2 mutations and Parkinson's disease: three questions

作者：Greggio Elisa; Cookson Mark R^*

来源：ASN Neuro, 2009, 1(1): e00002.

DOI：10.1042/AN20090007

• GTPase
• leucine-rich repeat kinase 2 (LRRK2)
• Lewy body
• neurotoxicity
• Parkinson's disease

Mutations in the gene encoding LRRK2 (leucine-rich repeat kinase 2) were first identified in 2004 and have since been shown to be the single most common cause of inherited Parkinson's disease. The protein is a large GTP-regulated serine/threonine kinase that additionally contains several protein-protein interaction domains. In the present review, we discuss three important, but unresolved, questions concerning LRRK2. We first ask: what is the normal function of LRRK2? Related to this, we discuss the evidence of LRRK2 activity as a GTPase and as a kinase and the available data on protein-protein interactions. Next we raise the question of how mutations affect LRRK2 function, focusing on some slightly controversial results related to the kinase activity of the protein in a variety of in vitro systems. Finally, we discuss what the possible mechanisms are for LRRK2-mediated neurotoxicity, in the context of known activities of the protein.

• 出版日期2009