title: Novel insights into the neurobiology underlying LRRK2-linked Parkinson's disease.
abstract: Mutations in LRRK2 (leucine-rich repeat kinase 2) are found associated with both sporadic and familial Parkinson's disease (PD). Pathogenic mutations are localized to the catalytic domains of LRRK2, including kinase and GTPase domains. Altered catalytic activity correlates with neurotoxicity, indicating that targeting those activities may provide clues as to novel therapeutic strategies for LRRK2-linked PD. However, the cellular readout of such altered catalytic activities remains largely unknown. Recent cell biological studies have started to highlight possible early cellular events which are altered in the presence of pathogenic LRRK2 and may ultimately lead to neuronal demise, and these studies link altered LRRK2 function to various abnormal endolysosomal vesicular trafficking events. This review examines our current knowledge of LRRK2 neurobiology and how pathogenic mutations may lead to neurodegeneration in PD.
authors.affiliation: Institute of Parasitology and Biomedicine "López-Neyra", Consejo Superior de Investigaciones Científicas (CSIC), Avda del Conocimiento s/n, 18016 Granada, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Gómez-Suaga
authors.affiliation: Institute of Parasitology and Biomedicine "López-Neyra", Consejo Superior de Investigaciones Científicas (CSIC), Avda del Conocimiento s/n, 18016 Granada, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Fdez
authors.affiliation: Institute of Parasitology and Biomedicine "López-Neyra", Consejo Superior de Investigaciones Científicas (CSIC), Avda del Conocimiento s/n, 18016 Granada, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Fernández
authors.affiliation: Institute of Parasitology and Biomedicine "López-Neyra", Consejo Superior de Investigaciones Científicas (CSIC), Avda del Conocimiento s/n, 18016 Granada, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Martínez-Salvador
authors.affiliation: Institute of Parasitology and Biomedicine "López-Neyra", Consejo Superior de Investigaciones Científicas (CSIC), Avda del Conocimiento s/n, 18016 Granada, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Blanca Ramírez
authors.affiliation: Institute of Parasitology and Biomedicine "López-Neyra", Consejo Superior de Investigaciones Científicas (CSIC), Avda del Conocimiento s/n, 18016 Granada, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Madero-Pérez
authors.affiliation: Institute of Parasitology and Biomedicine "López-Neyra", Consejo Superior de Investigaciones Científicas (CSIC), Avda del Conocimiento s/n, 18016 Granada, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Rivero-Ríos
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Genética, E. Enfermería y TO, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Universidad de Extremadura, Cáceres, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Fuentes
authors.affiliation: Institute of Parasitology and Biomedicine "López-Neyra", Consejo Superior de Investigaciones Científicas (CSIC), Avda del Conocimiento s/n, 18016 Granada, Spain. Electronic address: sabine.hilfiker@ipb.csic.es.
authors.forename: S
authors.initials: S
authors.lastname: Hilfiker
mesh_terms: D000818:Animals; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008959:Models, Neurological; D010300:Parkinson Disease / Q000201:enzymology* / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000201:enzymology / Q000235:genetics
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases
keywords: Autophagy; Endocytosis; GTPase; Inhibitor; Kinase; LRRK2; Neuronal dysfunction; Parkinson's disease; Rab protein; Vesicle trafficking