The biology and pathobiology of LRRK2: implications for Parkinson's disease.
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are an important cause of late-onset, familial and sporadic Parkinson's disease. LRRK2 is a large unique protein containing both GTPase and kinase enzymatic domains together with multiple protein-protein interaction domains. LRRK2 initially appears to function as a GTPase-regulated protein kinase. The majority of pathogenic mutations lead to enhanced kinase activity of LRRK2. Disease-associated mutations in LRRK2 also promote the formation of cytoplasmic inclusions and induce neuronal toxicity in cultured cells in a kinase-dependent manner. These and other important aspects of LRRK2 biology and pathophysiology are discussed in detail in this review.
Moore
Darren J
DJ
Institute for Cell Engineering and Department of Neurology, Johns Hopkins University School of Medicine, Broadway Research Building, 733 North Broadway, Baltimore, MD 21205, USA. djmoore@jhmi.edu
D000818:Animals; D001695:Biology; D020558:GTP Phosphohydrolases / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D002479:Inclusion Bodies / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism
C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D020558:GTP Phosphohydrolases