Leucine-rich repeat kinase 2 (LRRK2): A key player in the pathogenesis of Parkinson's disease

✍ Scribed by Payal N. Gandhi; Shu G. Chen; Amy L. Wilson-Delfosse

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 209 KB
• Volume: 87
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.21949

✦ Synopsis

Abstract

Parkinson's disease (PD) is the most common neurodegenerative movement disorder, with a prevalence of more than 1% after the age of 65 years. Mutations in the gene encoding leucine‐rich repeat kinase‐2 (LRRK2) have recently been linked to autosomal dominant, late‐onset PD that is clinically indistinguishable from typical, idiopathic disease. LRRK2 is a multidomain protein containing several protein interaction motifs as well as dual enzymatic domains of GTPase and protein kinase activities. Disease‐associated mutations are found throughout the multidomain structure of the protein. LRRK2, however, is unique among the PD‐causing genes, because a missense mutation, G2019S, is a frequent determinant of not only familial but also sporadic PD. Thus, LRRK2 has emerged as a promising therapeutic target for combating PD. In this Mini‐Review, we look at the current state of knowledge regarding the domain structure, amino acid substitutions, and potential functional roles of LRRK2. © 2008 Wiley‐Liss, Inc.