title: Mechanisms of LRRK2-mediated neurodegeneration.
abstract: Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene represent the most common cause of familial Parkinson's disease (PD), whereas common variation at the LRRK2 locus is associated with an increased risk of idiopathic PD. Considerable progress has been made toward understanding the biological functions of LRRK2 and the molecular mechanisms underlying the pathogenic effects of disease-associated mutations. The development of neuronal culture models and transgenic or viral-based rodent models have proved useful for identifying a number of emerging pathways implicated in LRRK2-dependent neuronal damage, including the microtubule network, actin cytoskeleton, autophagy, mitochondria, vesicular trafficking, and protein quality control. However, many important questions remain to be posed and answered. Elucidating the molecular mechanisms and pathways underlying LRRK2-mediated neurodegeneration is critical for the identification of new molecular targets for therapeutic intervention in PD. In this review we discuss recent advances and unanswered questions in understanding the pathophysiology of LRRK2.
authors.affiliation: Laboratory of Molecular Neurodegenerative Research, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne-EPFL, SV-BMI-LMNR, AI 2150, Station 15, 1015 Lausanne, Switzerland.
authors.forename: Elpida
authors.initials: E
authors.lastname: Tsika
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Moore
mesh_terms: D001343:Autophagy / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008928:Mitochondria / Q000235:genetics / Q000473:pathology; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics*; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases