LRRK2

Summary

Gene Symbol: LRRK2
Description: leucine rich repeat kinase 2
Alias: AURA17, DARDARIN, PARK8, RIPK7, ROCO2, leucine-rich repeat serine/threonine-protein kinase 2, augmented in rheumatoid arthritis 17
Species: human

Top Publications

  1. doi Phosphopeptide analysis reveals two discrete clusters of phosphorylation in the N-terminus and the Roc domain of the Parkinson-disease associated protein kinase LRRK2
    Christian Johannes Gloeckner
    Helmholtz Zentrum Munchen German Research Center for Environmental Health, Department of Protein Science, Neuherberg, Germany
    J Proteome Res 9:1738-45. 2010
  2. pmc The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson's disease
    Mark R Cookson
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health NIH, Building 35, Room 1A116, MSC 3707, 35 Convent Drive, Bethesda, Maryland 20982 3707, USA
    Nat Rev Neurosci 11:791-7. 2010
  3. doi Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease
    Wataru Satake
    Division of Neurology Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan
    Nat Genet 41:1303-7. 2009
  4. ncbi Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology
    Alexander Zimprich
    Department of Neurodegenerative Disease, Hertie Institute for Clinical Brain Research, University of Tubingen, 72076 Tubingen, Germany
    Neuron 44:601-7. 2004
  5. pmc Dopaminergic neuronal loss, reduced neurite complexity and autophagic abnormalities in transgenic mice expressing G2019S mutant LRRK2
    David Ramonet
    Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland
    PLoS ONE 6:e18568. 2011
  6. pmc RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson's disease risk
    David A MacLeod
    Department of Neurology and Taub Institute, Columbia University, Black Building 1208, 650 West 168th Street, New York, NY 10032, USA
    Neuron 77:425-39. 2013
  7. pmc Role of autophagy in G2019S-LRRK2-associated neurite shortening in differentiated SH-SY5Y cells
    Edward D Plowey
    Department of Pathology, Division of Neuropathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Neurochem 105:1048-56. 2008
  8. pmc Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity
    Andrew B West
    Institute for Cell Engineering, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 102:16842-7. 2005
  9. ncbi Kinase activity of mutant LRRK2 mediates neuronal toxicity
    Wanli W Smith
    Department of Psychiatry, Division of Neurobiology, Johns Hopkins University School of Medicine, CMSC 8 121, 600 North Wolfe Street, Baltimore, Maryland 21287, USA
    Nat Neurosci 9:1231-3. 2006
  10. doi LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool
    Giovanni Piccoli
    Department of Protein Science and Institute of Developmental Genetics, Helmholtz Zentrum Munchen, D 85764 Munich, Germany
    J Neurosci 31:2225-37. 2011

Research Grants

  1. Gene-environment interactions in transgenic rat models of Parkinson disease
    J Timothy Greenamyre; Fiscal Year: 2010
  2. Rachel Saunders-Pullman; Fiscal Year: 2015
  3. Functional Characterization of LRRK2 Knock-out and Knock-in Mouse Models
    Heather L Melrose; Fiscal Year: 2012
  4. Amy L Wilson-Delfosse; Fiscal Year: 2014
  5. Mechanisms of Selective Neurodegeneration in Parkinson Disease
    Xugang Xia; Fiscal Year: 2010
  6. The Cellular and Molecular Mechanisms of Parkinson's Disease
    FREDERICK CHARLES NUCIFORA; Fiscal Year: 2012
  7. JADA M LEWIS; Fiscal Year: 2016
  8. LRRK2 and mitochondrial dysfunction
    Xiongwei Zhu; Fiscal Year: 2011
  9. Andrew B West; Fiscal Year: 2016
  10. NATHANAEL SCHIANDER GRAY; Fiscal Year: 2015

Detail Information

Publications286 found, 100 shown here

  1. doi Phosphopeptide analysis reveals two discrete clusters of phosphorylation in the N-terminus and the Roc domain of the Parkinson-disease associated protein kinase LRRK2
    Christian Johannes Gloeckner
    Helmholtz Zentrum Munchen German Research Center for Environmental Health, Department of Protein Science, Neuherberg, Germany
    J Proteome Res 9:1738-45. 2010
    Mutations in leucine-rich repeat kinase 2 (LRRK2) that increase its kinase activity associate with familial forms of Parkinson disease (PD)...
  2. pmc The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson's disease
    Mark R Cookson
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health NIH, Building 35, Room 1A116, MSC 3707, 35 Convent Drive, Bethesda, Maryland 20982 3707, USA
    Nat Rev Neurosci 11:791-7. 2010
    ..Here, I discuss how mutations in a large complex gene--leucine-rich repeat kinase 2 (LRRK2)--affect protein function, and I review recent evidence that LRRK2 mutations affect pathways that involve other ..
  3. doi Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease
    Wataru Satake
    Division of Neurology Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan
    Nat Genet 41:1303-7. 2009
    ..94 x 10(-9)). We also detected strong associations at SNCA on 4q22 (P = 7.35 x 10(-17)) and LRRK2 on 12q12 (P = 2.72 x 10(-8)), both of which are implicated in autosomal dominant forms of parkinsonism...
  4. ncbi Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology
    Alexander Zimprich
    Department of Neurodegenerative Disease, Hertie Institute for Clinical Brain Research, University of Tubingen, 72076 Tubingen, Germany
    Neuron 44:601-7. 2004
    ..five missense and one putative splice site mutation) in a gene encoding a large, multifunctional protein, LRRK2 (leucine-rich repeat kinase 2)...
  5. pmc Dopaminergic neuronal loss, reduced neurite complexity and autophagic abnormalities in transgenic mice expressing G2019S mutant LRRK2
    David Ramonet
    Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland
    PLoS ONE 6:e18568. 2011
    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause late-onset, autosomal dominant familial Parkinson's disease (PD) and also contribute to idiopathic PD...
  6. pmc RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson's disease risk
    David A MacLeod
    Department of Neurology and Taub Institute, Columbia University, Black Building 1208, 650 West 168th Street, New York, NY 10032, USA
    Neuron 77:425-39. 2013
    ..Here we show that the consequences of variants at 2 such loci, PARK16 and LRRK2, are highly interrelated, both in terms of their broad impacts on human brain transcriptomes of unaffected ..
  7. pmc Role of autophagy in G2019S-LRRK2-associated neurite shortening in differentiated SH-SY5Y cells
    Edward D Plowey
    Department of Pathology, Division of Neuropathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Neurochem 105:1048-56. 2008
    ..a prominent feature of the degenerative phenotype associated with mutations in leucine rich repeat kinase 2 (LRRK2) that are implicated in autosomal dominant and some cases of sporadic Parkinson's disease...
  8. pmc Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity
    Andrew B West
    Institute for Cell Engineering, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 102:16842-7. 2005
    Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) cause late-onset Parkinson's disease (PD) with a clinical appearance indistinguishable from idiopathic PD...
  9. ncbi Kinase activity of mutant LRRK2 mediates neuronal toxicity
    Wanli W Smith
    Department of Psychiatry, Division of Neurobiology, Johns Hopkins University School of Medicine, CMSC 8 121, 600 North Wolfe Street, Baltimore, Maryland 21287, USA
    Nat Neurosci 9:1231-3. 2006
    Mutations in the the leucine-rich repeat kinase-2 (LRRK2) gene cause autosomal-dominant Parkinson disease and some cases of sporadic Parkinson disease...
  10. doi LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool
    Giovanni Piccoli
    Department of Protein Science and Institute of Developmental Genetics, Helmholtz Zentrum Munchen, D 85764 Munich, Germany
    J Neurosci 31:2225-37. 2011
    Mutations in leucine-rich repeat kinase 2 (LRRK2) are the single most common cause of inherited Parkinson's disease...
  11. doi LRRK2 regulates synaptic vesicle endocytosis
    Narae Shin
    Department of Life Science, GIST, Buk Gu, Gwangju, South Korea
    Exp Cell Res 314:2055-65. 2008
    The leucine-rich repeat kinase 2 (LRRK2) has been identified as the defective gene at the PARK8 locus causing the autosomal dominant form of Parkinson's disease (PD)...
  12. pmc Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson's disease
    Byoung Dae Lee
    Neuroregeneration Program, Institute for Cell Engineering, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Nat Med 16:998-1000. 2010
    Leucine-rich repeat kinase-2 (LRRK2) mutations are a common cause of Parkinson's disease. Here we identify inhibitors of LRRK2 kinase that are protective in in vitro and in vivo models of LRRK2-induced neurodegeneration...
  13. doi LRRK2 G2019S mutation induces dendrite degeneration through mislocalization and phosphorylation of tau by recruiting autoactivated GSK3ß
    Chin Hsien Lin
    Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan
    J Neurosci 30:13138-49. 2010
    ..features of Parkinson's disease (PD) with autosomal-dominant mutations in leucine-rich repeat kinase 2 (LRRK2)...
  14. pmc Membrane localization of LRRK2 is associated with increased formation of the highly active LRRK2 dimer and changes in its phosphorylation
    Zdenek Berger
    Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Biochemistry 49:5511-23. 2010
    Autosomal dominant mutations in leucine rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease (PD)...
  15. ncbi A comparative analysis of leucine-rich repeat kinase 2 (Lrrk2) expression in mouse brain and Lewy body disease
    H L Melrose
    Molecular Genetics Laboratory and Core, Morris K Udall Parkinson s Disease Research Center of Excellence, Mayo Clinic, Department of Neuroscience, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Neuroscience 147:1047-58. 2007
    Pathogenic substitutions in leucine-rich repeat kinase 2 (LRRK2, Lrrk2) have been genetically linked to familial, late-onset Parkinsonism...
  16. pmc 14-3-3 binding to LRRK2 is disrupted by multiple Parkinson's disease-associated mutations and regulates cytoplasmic localization
    R Jeremy Nichols
    University of Dundee, Scotland, UK
    Biochem J 430:393-404. 2010
    b>LRRK2 (leucine-rich repeat protein kinase 2) is mutated in a significant number of Parkinson's disease patients, but still little is understood about how it is regulated or functions...
  17. pmc LRRK2 is involved in the IFN-gamma response and host response to pathogens
    Agnès Gardet
    Center for the Study of the Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    J Immunol 185:5577-85. 2010
    b>LRRK2 was previously identified as a defective gene in Parkinson's disease, and it is also located in a risk region for Crohn's disease. In this study, we aim to determine whether LRRK2 could be involved in immune responses...
  18. pmc The Parkinson's disease kinase LRRK2 autophosphorylates its GTPase domain at multiple sites
    Elisa Greggio
    Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892 3707, USA
    Biochem Biophys Res Commun 389:449-54. 2009
    Mutations in leucine-rich repeat kinase 2 (LRRK2) are a common cause of inherited Parkinson's disease (PD). The protein is large and complex, but pathogenic mutations cluster in a region containing GTPase and kinase domains...
  19. pmc LRRK2 kinase activity is dependent on LRRK2 GTP binding capacity but independent of LRRK2 GTP binding
    Jean Marc Taymans
    Laboratory for Neurobiology and Gene Therapy, Katholieke Universiteit Leuven, Leuven, Belgium
    PLoS ONE 6:e23207. 2011
    Leucine rich repeat kinase 2 (LRRK2) is a Parkinson's disease (PD) gene that encodes a large multidomain protein including both a GTPase and a kinase domain...
  20. doi Mitochondrial impairment in patients with Parkinson disease with the G2019S mutation in LRRK2
    Heather Mortiboys
    Academic Neurology Unit, Medical School, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK
    Neurology 75:2017-20. 2010
    The LRRK2(G2019S) mutation is the most common identifiable cause for Parkinson disease (PD), but the underlying mechanisms leading to neuronal cell death remain largely unclear...
  21. pmc Dependence of leucine-rich repeat kinase 2 (LRRK2) kinase activity on dimerization
    Saurabh Sen
    Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
    J Biol Chem 284:36346-56. 2009
    Dominant missense mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common known genetic cause of Parkinson disease...
  22. doi The leucine rich repeat kinase 2 (LRRK2) G2019S substitution mutation. Association with Parkinson disease, malignant melanoma and prevalence in ethnic groups in Israel
    Sharon Hassin-Baer
    The Parkinson s Disease and Movement Disorders Clinic, Dept of Neurology and Sagol Neuroscience Center, Chaim Sheba Medical Center, Tel Hashomer, 52621, Israel
    J Neurol 256:483-7. 2009
    A single missense mutation (G2019S) in the leucine rich repeat kinase 2 (LRRK2) gene has been reported to be prevalent among Ashkenazi Jewish patients with Parkinson disease (PD)...
  23. pmc LRRK2 phosphorylates tubulin-associated tau but not the free molecule: LRRK2-mediated regulation of the tau-tubulin association and neurite outgrowth
    Fumitaka Kawakami
    Department of Biochemistry, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Japan
    PLoS ONE 7:e30834. 2012
    Leucine-rich repeat kinase 2 (LRRK2), a large protein kinase containing multi-functional domains, has been identified as the causal molecule for autosomal-dominant Parkinson's disease (PD)...
  24. doi Leucine-rich repeat kinase 2 functionally interacts with microtubules and kinase-dependently modulates cell migration
    Mareike Caesar
    Boehringer Ingelheim Pharma GmbH and Co KG, CNS Diseases Research, 88397 Biberach an der Riss, Germany
    Neurobiol Dis 54:280-8. 2013
    Recent studies indicate that the Parkinson's disease-linked leucine-rich repeat kinase 2 (LRRK2) modulates cytoskeletal functions by regulating actin and tubulin dynamics, thereby affecting neurite outgrowth...
  25. ncbi GTP binding is essential to the protein kinase activity of LRRK2, a causative gene product for familial Parkinson's disease
    Genta Ito
    Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7 3 1 Hongo, Bunkyoku, Tokyo, 113 0033 Japan
    Biochemistry 46:1380-8. 2007
    ..kinase 2 (LRRK2), a product of a causative gene for the autosomal-dominant form of familial Parkinson's disease (PARK8), harbors a Ras-like small GTP binding protein-like (ROC) domain besides the kinase domain, although the ..
  26. ncbi Variants in the LRRK1 gene and susceptibility to Parkinson's disease in Norway
    Kristoffer Haugarvoll
    Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida, USA, and Department of Neurology, St Olav s Hospital, Trondheim, Norway
    Neurosci Lett 416:299-301. 2007
    The discovery of LRRK2 gene mutations in late-onset Parkinson's disease (PD) has irrevocably established the role of genetics in the etiology of PD. The LRRK1 gene is the single homolog of LRRK2...
  27. pmc The R1441C mutation of LRRK2 disrupts GTP hydrolysis
    Patrick A Lewis
    Laboratory of Neurogenetics, National Institute on Aging, 35 Convent Drive, Bethesda, MD 20892 3707, USA
    Biochem Biophys Res Commun 357:668-71. 2007
    Mutations in Leucine Rich Repeat Kinase 2 (LRRK2) are the leading genetic cause of Parkinson's disease (PD)...
  28. pmc LRRK2 and the stress response: interaction with MKKs and JNK-interacting proteins
    C H Hsu
    Department of Pharmacology, Boston University School of Medicine, Boston, MA, USA
    Neurodegener Dis 7:68-75. 2010
    Increasing evidence supports a putative link between LRRK2 function and the MAP kinase cascades. We recently demonstrated that LRRK2 binds to MKK6, -3, and -7...
  29. doi Identification of the autophosphorylation sites of LRRK2
    Shogo Kamikawaji
    Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7 3 1 Hongo, Bunkyoku, Tokyo, 113 0033 Japan
    Biochemistry 48:10963-75. 2009
    ..A subset of patients develop PD as an autosomal dominant trait, of which PARK8 caused by mutations in the leucine-rich repeat kinase 2 (LRRK2) gene is highlighted because of its high frequency ..
  30. pmc GTPase activity plays a key role in the pathobiology of LRRK2
    Yulan Xiong
    Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
    PLoS Genet 6:e1000902. 2010
    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are associated with late-onset, autosomal-dominant, familial Parkinson's disease (PD) and also contribute to sporadic disease...
  31. pmc LRRK2 modulates vulnerability to mitochondrial dysfunction in Caenorhabditis elegans
    Shamol Saha
    Department of Pharmacology, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    J Neurosci 29:9210-8. 2009
    Mutations in leucine-rich repeat kinase 2 (LRRK2) cause autosomal-dominant familial Parkinson's disease. We generated lines of Caenorhabditis elegans expressing neuronally directed human LRRK2...
  32. pmc LRRK2 Parkinson disease mutations enhance its microtubule association
    Lauren R Kett
    Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA
    Hum Mol Genet 21:890-9. 2012
    Dominant missense mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic causes of Parkinson disease (PD) and genome-wide association studies identify LRRK2 sequence variants as risk factors for sporadic PD...
  33. pmc LRRK2 phosphorylates moesin at threonine-558: characterization of how Parkinson's disease mutants affect kinase activity
    Mahaboobi Jaleel
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 405:307-17. 2007
    Mutations in the LRRK2 (leucine-rich repeat kinase-2) gene cause late-onset PD (Parkinson's disease)...
  34. pmc The WD40 domain is required for LRRK2 neurotoxicity
    Nathan D Jorgensen
    Department of Neurology, Columbia University Medical Center, New York, New York, United States of America
    PLoS ONE 4:e8463. 2009
    Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson disease (PD)...
  35. pmc Insight into the mode of action of the LRRK2 Y1699C pathogenic mutant
    Veronique Daniëls
    Laboratory for Neurobiology and Gene Therapy, Division of Molecular Medicine, Department of Molecular and Cellular Medicine, Katholieke Universiteit Leuven, Leuven, Belgium
    J Neurochem 116:304-15. 2011
    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most prevalent known cause of autosomal dominant Parkinson's disease...
  36. pmc The chaperone activity of heat shock protein 90 is critical for maintaining the stability of leucine-rich repeat kinase 2
    Lizhen Wang
    Unit of Transgenesis, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland 20892, USA
    J Neurosci 28:3384-91. 2008
    ..the majority of PD cases are sporadic, some are inherited, including those caused by leucine-rich repeat kinase 2 (LRRK2) mutations...
  37. doi Investigation of leucine-rich repeat kinase 2 : enzymological properties and novel assays
    Vasanti S Anand
    Wyeth Research, Discovery Neuroscience, Princeton, NJ 08543, USA
    FEBS J 276:466-78. 2009
    Mutations in leucine-rich repeat kinase 2 (LRRK2) comprise the leading cause of autosomal dominant Parkinson's disease, with age of onset and symptoms identical to those of idiopathic forms of the disorder...
  38. ncbi Localization of LRRK2 to membranous and vesicular structures in mammalian brain
    Saskia Biskup
    Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Ann Neurol 60:557-69. 2006
    ..for late-onset autosomal dominant Parkinson's disease encodes a large novel protein of unknown biological function termed leucine-rich repeat kinase 2 (LRRK2). The studies herein explore the localization of LRRK2 in the mammalian brain.
  39. pmc A direct interaction between leucine-rich repeat kinase 2 and specific β-tubulin isoforms regulates tubulin acetylation
    Bernard M H Law
    From the Department of Pharmacology, UCL School of Pharmacy, University College London 29 39 Brunswick Square, London WC1N 1AX, United Kingdom
    J Biol Chem 289:895-908. 2014
    Mutations in LRRK2, encoding the multifunctional protein leucine-rich repeat kinase 2 (LRRK2), are a common cause of Parkinson disease...
  40. pmc Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease
    Alexandria Beilina
    Cell Biology and Gene Expression Section, Computational Biology Core, Laboratory of Neurogenetics, and Molecular Genetics Section, National Institute on Aging National Institutes of Health, Bethesda, MD 20892
    Proc Natl Acad Sci U S A 111:2626-31. 2014
    Mutations in leucine-rich repeat kinase 2 (LRRK2) cause inherited Parkinson disease (PD), and common variants around LRRK2 are a risk factor for sporadic PD...
  41. doi LRRK2 expression in idiopathic and G2019S positive Parkinson's disease subjects: a morphological and quantitative study
    S Sharma
    Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, UCL, London, UK
    Neuropathol Appl Neurobiol 37:777-90. 2011
    Mutations in the gene encoding leucine-rich repeat kinase-2 (LRRK2) have been established as a common genetic cause of Parkinson's disease (PD)...
  42. pmc Temporal expression of mutant LRRK2 in adult rats impairs dopamine reuptake
    Hongxia Zhou
    Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
    Int J Biol Sci 7:753-61. 2011
    ..Mutation of the leucine-rich repeat kinase-2 (LRRK2) gene is associated with familial and sporadic PD, as exemplified by G2019S substitution...
  43. pmc Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: a case-control study
    Owen A Ross
    Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA
    Lancet Neurol 10:898-908. 2011
    Background The leucine-rich repeat kinase 2 gene (LRRK2) harbours highly penetrant mutations that are linked to familial parkinsonism...
  44. doi Re-examination of the dimerization state of leucine-rich repeat kinase 2: predominance of the monomeric form
    Genta Ito
    Department of Neuropathology, Graduate School of Medicine, University of Tokyo, 7 3 1 Hongo, Bunkyoku, Tokyo 113 0033, Japan
    Biochem J 441:987-94. 2012
    Mutations in the LRRK2 (leucine-rich repeat kinase 2) gene have been identified in PARK8, a major form of autosomal-dominantly inherited familial Parkinson's disease, although the biochemical properties of LRRK2 are not fully understood...
  45. doi Leucine-rich repeat kinase 2 (LRRK2) cellular biology: a review of recent advances in identifying physiological substrates and cellular functions
    Robert E Drolet
    Department of Neurosymptomatic Disorders, Department of Chemistry, Modeling, and Informatics, Merck Research Laboratories, Merck and Co, West Point, PA 19486, USA
    J Neurogenet 25:140-51. 2011
    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common forms of inheritable Parkinson's disease and likely play a role in sporadic disease as well...
  46. pmc Regulation of physiologic actions of LRRK2: focus on autophagy
    Andrew Ferree
    Department of Pharmacology, Boston University School of Medicine, Boston, Mass 02118 2526, USA
    Neurodegener Dis 10:238-41. 2012
    Mutations in LRRK2 are associated with familial and sporadic Parkinson's disease (PD). Subjects with PD caused by LRRK2 mutations show pleiotropic pathology that can involve inclusions containing α-synuclein, tau or neither protein...
  47. doi Leucine-rich repeat kinase 2 is associated with the endoplasmic reticulum in dopaminergic neurons and accumulates in the core of Lewy bodies in Parkinson disease
    Jérémie Vitte
    Laboratory of Molecular Basis, Physiopathology and Treatment of Neurodegenerative Diseases, Universite Pierre et Marie Curie Paris 6, Centre de Recherche de l Institut du Cerveau et de la Moelle Epiniere, UMR S975, Paris, France
    J Neuropathol Exp Neurol 69:959-72. 2010
    Mutation of the leucine-rich repeat kinase 2 (LRRK2) gene is the most frequent genetic cause of Parkinson disease (PD)...
  48. doi Leucine-rich repeat kinase 2 phosphorylates brain tubulin-beta isoforms and modulates microtubule stability--a point of convergence in parkinsonian neurodegeneration?
    Frank Gillardon
    Boehringer Ingelheim Pharma GmbH and Co KG, Birkendorfer Str 65, 88397 Biberach an der Riss, Germany
    J Neurochem 110:1514-22. 2009
    Autosomal dominant mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of late-onset Parkinson's disease...
  49. doi LRRK2 in Parkinson's disease: genetic and clinical studies from patients
    Udhaya Kumari
    Department of Neurology, Singapore General Hospital, Singapore, Singapore
    FEBS J 276:6455-63. 2009
    Mutations in leucine-rich repeat kinase 2 (LRRK2) (PARK8) are associated with both familial and sporadic forms of Parkinson's disease...
  50. doi Lrrk2 phosphorylates alpha synuclein at serine 129: Parkinson disease implications
    Hong Qing
    Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada
    Biochem Biophys Res Commun 387:149-52. 2009
    ..potent cause of autosomal dominant Parkinson disease (PD) while mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause...
  51. ncbi The Parkinson disease gene LRRK2: evolutionary and structural insights
    Ignacio Marín
    Departamento de Genetica, Universidad de Valencia, Burjassot, Spain
    Mol Biol Evol 23:2423-33. 2006
    Mutations in the human leucine-rich repeat kinase 2 (LRRK2) gene are associated with both familial and sporadic Parkinson disease (PD). LRRK2 belongs to a gene family known as Roco...
  52. ncbi Lrrk2 G2385R is an ancestral risk factor for Parkinson's disease in Asia
    Matthew J Farrer
    Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Parkinsonism Relat Disord 13:89-92. 2007
    ..The leucine-rich repeat kinase 2 (Lrrk2) G2385R substitution is associated with familial parkinsonism, late-, and early-onset Parkinson's disease in ..
  53. pmc The Parkinson's disease associated LRRK2 exhibits weaker in vitro phosphorylation of 4E-BP compared to autophosphorylation
    Azad Kumar
    Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS ONE 5:e8730. 2010
    Mutations in the gene encoding Leucine-rich repeat kinase 2 (LRRK2) are the most common cause of inherited Parkinson's disease (PD)...
  54. doi Homo- and heterodimerization of ROCO kinases: LRRK2 kinase inhibition by the LRRK2 ROCO fragment
    Christian L Klein
    Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University Clinics Tübingen, Germany
    J Neurochem 111:703-15. 2009
    Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) are the most common cause of autosomal-dominant familial and late-onset sporadic Parkinson's disease (PD)...
  55. ncbi Leucine-rich repeat kinase 2 associates with lipid rafts
    Taku Hatano
    Department of Neurology, Juntendo University School of Medicine, Bunkyo, Tokyo, Japan
    Hum Mol Genet 16:678-90. 2007
    Leucine-Rich Repeat Kinase 2 (LRRK2) is a causative gene for the autosomal dominant form of Parkinson's disease (PD)...
  56. ncbi The LRRK2 G2019S mutation in Ashkenazi Jews with Parkinson disease: is there a gender effect?
    A Orr-Urtreger
    Genetic Institute, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv 64239, Israel
    Neurology 69:1595-602. 2007
    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common genetic determinant of Parkinson disease (PD) identified to date, and have been implicated in both familial and sporadic forms of the disease...
  57. pmc LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model
    Javier Alegre-Abarrategui
    Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK
    Hum Mol Genet 18:4022-34. 2009
    Leucine rich repeat kinase 2 (LRRK2) mutations are the most common genetic cause of Parkinson's disease (PD) although LRRK2 function remains unclear...
  58. pmc LRRK2 G2019S mutations are associated with an increased cancer risk in Parkinson disease
    Rachel Saunders-Pullman
    Department of Neurology, Beth Israel Medical Center, New York, New York, USA
    Mov Disord 25:2536-41. 2010
    Leucine rich repeat kinase (LRRK2) G2019S mutations are presumed to cause PD through a toxic gain of function of the protein kinase...
  59. ncbi Localization of Parkinson's disease-associated LRRK2 in normal and pathological human brain
    Shinji Higashi
    Laboratory of Molecular Neuroscience, The Babraham Institute, Babraham, Cambridge, UK
    Brain Res 1155:208-19. 2007
    Mutations in the LRRK2 gene cause autosomal dominant, late-onset parkinsonism, which presents with pleomorphic pathology including alpha-synucleopathy...
  60. pmc The Parkinson disease-associated leucine-rich repeat kinase 2 (LRRK2) is a dimer that undergoes intramolecular autophosphorylation
    Elisa Greggio
    Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, NIA, National Institutes of Health, Bethesda, MD 20892, USA
    J Biol Chem 283:16906-14. 2008
    Mutations in leucine-rich repeat kinase 2 (LRRK2) are a common cause of familial and apparently sporadic Parkinson disease. LRRK2 is a multidomain protein kinase with autophosphorylation activity...
  61. ncbi The importance of Wnt signalling for neurodegeneration in Parkinson's disease
    Daniel C Berwick
    Department of Pharmacology, UCL School of Pharmacy, University College London, 29 39 Brunswick Square, London WC1N 1AX, U K
    Biochem Soc Trans 40:1123-8. 2012
    ..This suggests the prospect of targeting Wnt signalling pathways to modify PD progression...
  62. doi GTPase activity regulates kinase activity and cellular phenotypes of Parkinson's disease-associated LRRK2
    Alice Biosa
    Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fe de rale de Lausanne EPFL, Lausanne 1015, Switzerland
    Hum Mol Genet 22:1140-56. 2013
    Mutations in the LRRK2 gene cause autosomal dominant Parkinson's disease. LRRK2 encodes a multi-domain protein containing a Ras-of-complex (Roc) GTPase domain, a C-terminal of Roc domain and a protein kinase domain...
  63. pmc LRRK2 affects vesicle trafficking, neurotransmitter extracellular level and membrane receptor localization
    Rossana Migheli
    Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy
    PLoS ONE 8:e77198. 2013
    The leucine-rich repeat kinase 2 (LRRK2) gene was found to play a role in the pathogenesis of both familial and sporadic Parkinson's disease (PD). LRRK2 encodes a large multi-domain protein that is expressed in different tissues...
  64. ncbi Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease
    Coro Paisan-Ruiz
    Unitat de Genetica Molecular, Departament de Genòmica i Proteòmica, Institut de Biomedicina de València CSIC, E46010 Valencia, Spain
    Neuron 44:595-600. 2004
    ..Because of the tremor observed in PD and because a number of the families are of Basque descent, we have named this protein dardarin, derived from the Basque word dardara, meaning tremor.
  65. pmc Lrrk2 R1441C parkinsonism is clinically similar to sporadic Parkinson disease
    K Haugarvoll
    Department of Neurology, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA
    Neurology 70:1456-60. 2008
    Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common cause of Parkinson disease (PD). Several dominantly inherited pathogenic substitutions have been identified in different domains of the Lrrk2 protein...
  66. pmc LRRK2 kinase regulates synaptic morphology through distinct substrates at the presynaptic and postsynaptic compartments of the Drosophila neuromuscular junction
    Seongsoo Lee
    Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA
    J Neurosci 30:16959-69. 2010
    Mutations in leucine-rich repeat kinase 2 (LRRK2) are linked to familial as well as sporadic forms of Parkinson's disease (PD), a neurodegenerative disease characterized by dysfunction and degeneration of dopaminergic and other types of ..
  67. doi Clinical and brain imaging characteristics in leucine-rich repeat kinase 2-associated PD and asymptomatic mutation carriers
    Kathrin Brockmann
    Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tubingen, Tubingen, Germany
    Mov Disord 26:2335-42. 2011
    The objective of this research was to evaluate a possible endophenotype in leucine-rich repeat kinase 2 (LRRK2)-associated Parkinson's disease (PD)...
  68. pmc Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP
    Patricia Gómez-Suaga
    Institute of Parasitology and Biomedicine Lo pez Neyra, Consejo Superior de Investigaciones Cientificas, Avda del Conocimiento s n, 18100 Granada, Spain
    Hum Mol Genet 21:511-25. 2012
    Mutations in the leucine-rich repeat kinase-2 (LRRK2) gene cause late-onset Parkinson's disease, but its physiological function has remained largely unknown...
  69. pmc LRRK2 regulates mitochondrial dynamics and function through direct interaction with DLP1
    Xinglong Wang
    Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Hum Mol Genet 21:1931-44. 2012
    The leucine-rich repeat kinase 2 (LRRK2) mutations are the most common cause of autosomal-dominant Parkinson disease (PD). Mitochondrial dysfunction represents a critical event in the pathogenesis of PD...
  70. pmc LRRK2 inhibition attenuates microglial inflammatory responses
    Mark S Moehle
    Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
    J Neurosci 32:1602-11. 2012
    Missense mutations in leucine-rich repeat kinase 2 (LRRK2) cause late-onset Parkinson's disease (PD), and common genetic variation in LRRK2 modifies susceptibility to Crohn's disease and leprosy...
  71. doi Parkinson's disease-linked leucine-rich repeat kinase 2(R1441G) mutation increases proinflammatory cytokine release from activated primary microglial cells and resultant neurotoxicity
    F Gillardon
    Boehringer Ingelheim Pharma GmbH and Co KG, CNS Research, Birkendorfer Strasse 65, 88397 Biberach, Germany
    Neuroscience 208:41-8. 2012
    Mutations in leucine-rich repeat kinase 2 (LRRK2) have been causally linked to neuronal cell death in Parkinson's disease. LRRK2 expression has also been detected in B lymphocytes and macrophages, suggesting a role in immune responses...
  72. doi Leucine-rich repeat kinase 2 disturbs mitochondrial dynamics via Dynamin-like protein
    Jingwen Niu
    The National Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
    J Neurochem 122:650-8. 2012
    Mutations in Leucine-rich repeat kinase 2 (LRRK2) are the leading causes of genetically inherited Parkinson's disease (PD) identified so far...
  73. pmc Cellular effects of LRRK2 mutations
    Mark R Cookson
    Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, 35 Convent Drive, Bethesda, MD 20892 3707, USA
    Biochem Soc Trans 40:1070-3. 2012
    Mutations in LRRK2 (leucine-rich repeat kinase 2) are a relatively common cause of inherited PD (Parkinson's disease), but the mechanism(s) by which mutations lead to disease are poorly understood...
  74. pmc Phosphorylation of 4E-BP1 in the mammalian brain is not altered by LRRK2 expression or pathogenic mutations
    Alzbeta Trancikova
    Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland
    PLoS ONE 7:e47784. 2012
    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are a common cause of autosomal dominant familial Parkinson's disease (PD). LRRK2 encodes a multi-domain protein containing GTPase and kinase enzymatic domains...
  75. pmc Interplay of LRRK2 with chaperone-mediated autophagy
    Samantha J Orenstein
    Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, USA
    Nat Neurosci 16:394-406. 2013
    Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson's disease...
  76. pmc Parkinson-related LRRK2 mutation R1441C/G/H impairs PKA phosphorylation of LRRK2 and disrupts its interaction with 14-3-3
    Kathrin Muda
    Department of Biochemistry, University of Kassel, 34132 Kassel, Germany
    Proc Natl Acad Sci U S A 111:E34-43. 2014
    Leucine-rich repeat kinase 2 (LRRK2) is a multidomain protein implicated in Parkinson disease (PD); however, the molecular mechanism and mode of action of this protein remain elusive...
  77. pmc Mutant LRRK2 toxicity in neurons depends on LRRK2 levels and synuclein but not kinase activity or inclusion bodies
    Gaia Skibinski
    Gladstone Institute of Neurological Disease, the Taube Koret Center for Neurodegenerative Disease Research, and the Hellman Family Foundation Program in Alzheimer s Disease Research, San Francisco, California 94158, Departments of Neurology, Physiology, and Graduate Programs in Neuroscience and Biomedical Sciences, University of California, San Francisco, California 94158, and Laboratory of Neurogenetics, National Institutes of Health, Bethesda, Maryland 20892
    J Neurosci 34:418-33. 2014
    ..underlying the most common known cause of Parkinson's disease (PD), mutations in leucine-rich repeat kinase 2 (LRRK2)...
  78. pmc LRRK2 regulates synaptogenesis and dopamine receptor activation through modulation of PKA activity
    Loukia Parisiadou
    1 Transgenics Section, Laboratory of Neurogenetics, National Institute on Aging, US National Institutes of Health, Bethesda, Maryland, USA 2 Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA 3
    Nat Neurosci 17:367-76. 2014
    Leucine-rich repeat kinase 2 (LRRK2) is enriched in the striatal projection neurons (SPNs)...
  79. ncbi Apoptotic mechanisms in mutant LRRK2-mediated cell death
    Ciro Iaccarino
    Department of Physiological, Biochemical, and Cell Science, University of Sassari, Via Muroni 25, 07100 Sassari, Italy
    Hum Mol Genet 16:1319-26. 2007
    Mutations in the gene coding for leucine-rich repeat kinase 2 (LRRK2) cause autosomal-dominant Parkinson's disease...
  80. doi Developmental regulation of leucine-rich repeat kinase 1 and 2 expression in the brain and other rodent and human organs: Implications for Parkinson's disease
    M Westerlund
    Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden
    Neuroscience 152:429-36. 2008
    Mutations in leucine-rich repeat kinase 2 (LRRK2) constitute the most common known cause of Parkinson's disease (PD), accounting for both familial and sporadic forms of the disease...
  81. pmc Familial parkinsonism: study of original Sagamihara PARK8 (I2020T) kindred with variable clinicopathologic outcomes
    Kazuko Hasegawa
    Division of Neurology, National Hospital Organization, Sagamihara National Hospital, Japan
    Parkinsonism Relat Disord 15:300-6. 2009
    Since the causative gene linked to PARK8 parkinsonism was identified as LRRK2, LRRK2 gene mutations have been found to occur in about 4% of patients with hereditary Parkinson disease (PD); this percentage is even higher in certain ..
  82. pmc The G2019S pathogenic mutation disrupts sensitivity of leucine-rich repeat kinase 2 to manganese kinase inhibition
    Jason P Covy
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6084, USA
    J Neurochem 115:36-46. 2010
    Mutations in leucine-rich repeat kinase-2 (LRRK2) are the most common cause of late-onset Parkinson disease...
  83. pmc Signal transduction protein array analysis links LRRK2 to Ste20 kinases and PKC zeta that modulate neuronal plasticity
    Susanne Zach
    Boehringer Ingelheim Pharma GmbH and Co KG, CNS Research, Biberach an der Riss, Germany
    PLoS ONE 5:e13191. 2010
    Dominant mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease, however, the underlying pathogenic mechanisms are poorly understood...
  84. doi Transcriptional profile of Parkinson blood mononuclear cells with LRRK2 mutation
    Eugénie Mutez
    Univ Lille Nord de France, F 59000 Lille, France
    Neurobiol Aging 32:1839-48. 2011
    ..healthy controls and from Parkinson's disease (PD) patients carrying the most frequently found mutation of the LRRK2 gene (G2019S)...
  85. pmc Reevaluation of phosphorylation sites in the Parkinson disease-associated leucine-rich repeat kinase 2
    Xiaojie Li
    Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Biol Chem 285:29569-76. 2010
    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been identified as an important cause of late-onset, autosomal dominant familial Parkinson disease and contribute to sporadic Parkinson disease...
  86. ncbi MAPK-pathway activity, Lrrk2 G2019S, and Parkinson's disease
    Linda R White
    Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway
    J Neurosci Res 85:1288-94. 2007
    The 6055G>A mutation in the leucine-rich repeat kinase 2 (LRRK2) gene results in a G2019S substitution in the mixed-lineage kinase domain of Lrrk2, causing autosomal dominant Parkinson's disease (PD)...
  87. doi Neuropathology of Parkinson's disease with the R1441G mutation in LRRK2
    José Félix Martí-Massó
    Department of Neurology, Hospital Donostia, Paseo Dr Beguiristain s n, 20014 Donostia, San Sebastian, Gipuzkoa, Spain
    Mov Disord 24:1998-2001. 2009
    ..the neuropathological findings in a patient with Parkinson's disease (PD) associated with Basque R1441G-LRRK2/dardarin mutation...
  88. doi I(2020)T leucine-rich repeat kinase 2, the causative mutant molecule of familial Parkinson's disease, has a higher intracellular degradation rate than the wild-type molecule
    Etsuro Ohta
    Division of Clinical Immunology, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Kanagawa 228 8555, Japan
    Biochem Biophys Res Commun 390:710-5. 2009
    Leucine-rich repeat kinase 2 (LRRK2) has been identified as the causal gene for autosomal dominant familial Parkinson's disease (PD), although the mechanism of neurodegeneration involving the mutant LRRK2 molecules remains unknown...
  89. pmc Rac1 protein rescues neurite retraction caused by G2019S leucine-rich repeat kinase 2 (LRRK2)
    Diane Chan
    Department of Pharmacology, Boston University School of Medicine, Boston, Massachusetts 02118 2526, USA
    J Biol Chem 286:16140-9. 2011
    Mutations in leucine-rich repeat kinase 2 (LRRK2) are currently the most common genetic cause of familial late-onset Parkinson disease, which is clinically indistinguishable from idiopathic disease...
  90. pmc LRRK2-mediated neurodegeneration and dysfunction of dopaminergic neurons in a Caenorhabditis elegans model of Parkinson's disease
    Chen Yao
    Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA
    Neurobiol Dis 40:73-81. 2010
    Mutations in LRRK2 are thus far the most frequent known cause of autosomal dominant and idiopathic Parkinson's disease (PD) with prevalent mutations being found within the GTPase (R1441C/G) and kinase (G2019S) domains...
  91. doi Hyposmia in G2019S LRRK2-related parkinsonism: clinical and pathologic data
    L Silveira-Moriyama
    Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, UK
    Neurology 71:1021-6. 2008
    Mutations in PARK8 (LRRK2) are associated with autosomal dominant parkinsonism and Parkinson disease (PD)...
  92. pmc Progression of dopaminergic dysfunction in a LRRK2 kindred: a multitracer PET study
    R Nandhagopal
    Pacific Parkinson s Research Centre, Vancouver, BC, Canada V6T2B5
    Neurology 71:1790-5. 2008
    Little is known about the progression of dopaminergic dysfunction in LRRK2-associated Parkinson disease (PD)...
  93. doi Interaction of elongation factor 1-alpha with leucine-rich repeat kinase 2 impairs kinase activity and microtubule bundling in vitro
    F Gillardon
    Boehringer Ingelheim Pharma GmbH and Co KG, CNS Research, Birkendorfer St 65, 88397 Biberach an der Riss, Germany
    Neuroscience 163:533-9. 2009
    Autosomal dominant mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of late-onset Parkinson's disease...
  94. pmc Leucine-rich repeat kinase 2 mutations and Parkinson's disease: three questions
    Elisa Greggio
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20982 3707, USA
    ASN Neuro 1:. 2009
    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...
  95. pmc Mutations in the LRRK2 Roc-COR tandem domain link Parkinson's disease to Wnt signalling pathways
    Rosa M Sancho
    Department of Pharmacology, The School of Pharmacy, Brunswick Square, London, UK
    Hum Mol Genet 18:3955-68. 2009
    Mutations in PARK8, encoding LRRK2, are the most common known cause of Parkinson's disease. The LRRK2 Roc-COR tandem domain exhibits GTPase activity controlling LRRK2 kinase activity via an intramolecular process...
  96. pmc Leucine-rich repeat kinase 2 gene-associated disease: redefining genotype-phenotype correlation
    Christian Wider
    Department of Neurology, Mayo Clinic, Jacksonville, FL, USA
    Neurodegener Dis 7:175-9. 2010
    Leucine-rich repeat kinase 2 (LRRK2) has emerged as the most prevalent genetic cause of Parkinson's disease (PD) among Caucasians...
  97. ncbi Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity
    Andrew B West
    Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Hum Mol Genet 16:223-32. 2007
    Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) cause late-onset Parkinson's disease indistinguishable from idiopathic disease...
  98. ncbi Mutations in LRRK2/dardarin associated with Parkinson disease are more toxic than equivalent mutations in the homologous kinase LRRK1
    Elisa Greggio
    Cell Biology and Gene Expression Unit, National Institute on Aging, Bethesda, Maryland 20982 3707, USA
    J Neurochem 102:93-102. 2007
    Several mutations have been found in the leucine-rich repeat kinase 2 gene (LRRK2), encoding the protein dardarin, which are associated with autosomal dominant Parkinson disease...
  99. pmc Abnormal localization of leucine-rich repeat kinase 2 to the endosomal-lysosomal compartment in lewy body disease
    Shinji Higashi
    PET CT Dementia Research Center, Juntendo Tokyo Koto Geriatric Medical Center, Juntendo University School of Medicine, Koto ku, Tokyo, Japan
    J Neuropathol Exp Neurol 68:994-1005. 2009
    Missense mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common causes of both familial and sporadic forms of Parkinson disease and are also associated with diverse pathological alterations...
  100. pmc Leucine-rich repeat kinase 2 induces alpha-synuclein expression via the extracellular signal-regulated kinase pathway
    Iria Carballo-Carbajal
    Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University Clinics Tübingen, Germany
    Cell Signal 22:821-7. 2010
    Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most frequent cause of autosomal-dominant Parkinson's disease (PD)...
  101. ncbi LRRK2 mutations in Spanish patients with Parkinson disease: frequency, clinical features, and incomplete penetrance
    Carles Gaig
    Movement Disorders Unit, Neurology Service, Institut Clínic de Neurociències, Hospital Clinic, Institut d Investigacions Biomediques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain
    Arch Neurol 63:377-82. 2006
    Several pathogenic mutations in the LRRK2 gene have been implicated in familial and sporadic cases of Parkinson disease (PD)...

Research Grants79

  1. Gene-environment interactions in transgenic rat models of Parkinson disease
    J Timothy Greenamyre; Fiscal Year: 2010
    ..Specifically, we have created Tg rats that overexpress WT and mutant human alpha-synuclein (AS) and mutant LRRK2. Increased expression of WT AS from gene dupli- &triplications causes PD, and promoter polymorphisms that ..
  2. Rachel Saunders-Pullman; Fiscal Year: 2015
    ..The discovery that mutations in the leucine rich repeat kinase kinase (LRRK2) gene comprise the most common monogenic etiology of Parkinson disease (PD) provides an opportunity to address ..
  3. Functional Characterization of LRRK2 Knock-out and Knock-in Mouse Models
    Heather L Melrose; Fiscal Year: 2012
    ..Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) are the most frequent genetic cause of autosomal dominant Parkinsonism...
  4. Amy L Wilson-Delfosse; Fiscal Year: 2014
    ..isoform of Grx in mammals, leads to exacerbation of dopaminergic degeneration elicited by overexpression of mutant LRRK2 (G2019S or R1441C), [unreadable]-synuclein, or tyrosine hydroxylase...
  5. Mechanisms of Selective Neurodegeneration in Parkinson Disease
    Xugang Xia; Fiscal Year: 2010
    ..While pathogenic mutations in the alpha-synuclein or the LRRK2 gene gain toxic properties, mutations in the neuron-protective genes (i.e...
  6. The Cellular and Molecular Mechanisms of Parkinson's Disease
    FREDERICK CHARLES NUCIFORA; Fiscal Year: 2012
    ..My intention is to develop these skills by elucidating the pathogenesis of LRRK2-induced Parkinson's disease...
  7. JADA M LEWIS; Fiscal Year: 2016
    ..More recently, pathological studies of individuals carrying PD-linked mutations in the LRRK2 gene have shown tau pathology in a subset of mutation carriers...
  8. LRRK2 and mitochondrial dysfunction
    Xiongwei Zhu; Fiscal Year: 2011
    DESCRIPTION (provided by applicant): Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause thus far identified for both familial and idiopathic Parkinson's disease (PD)...
  9. Andrew B West; Fiscal Year: 2016
    ..Dominant missense mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common known specific cause of PD, and LRRK2 mutations associate with disease phenotypes that ..
  10. NATHANAEL SCHIANDER GRAY; Fiscal Year: 2015
    ..Our laboratory has had considerable success in developing first-in-class inhibitors of ALK, Mps1, Erk5, mTor, LRRK2, FGFRs, JNKs, and the T790M mutant form of EGFR and in using these compounds to validate new cancer targets...
  11. Richard A Firtel; Fiscal Year: 2015
    ..We have shown that Rab1A binds to and is required to activate Roco2, a member of the Roco family of GTPase-containing protein kinases...
  12. Structural insights into the mechanism of the novel dimeric ROC GTPase from LRRK2
    Junpeng Deng; Fiscal Year: 2009
    Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of Parkinson's disease (PD)...
  13. Role of NADPH oxidase 1-derived ROS in the pathogenesis of Parkinson's disease
    Yoon Seong Kim; Fiscal Year: 2012
    ..b>LRRK2 mutation (G2019S) increased ROS generation in N27 DA cells and apocynin, a specific NADPH oxidase inhibitor ..
  14. Pesticide Interactions in LRRK2 Transgenic Models
    AMY BEATRICE MANNING BOG; Fiscal Year: 2010
    ..Specifically, we will investigate the LRRK2 protein as a common mechanistic link between neurodegenerative conditions with parkinsonism...
  15. A Novel Monkey Model for Parkinson's Drug Discovery
    Howard J Federoff; Fiscal Year: 2010
    ..Among familial forms, mutations in the LRRK2 are most common contributing to over 10% of autosomal dominant familial PD and 3.6% of sporadic cases...
  16. JENNA MAE TABOR-GODWIN; Fiscal Year: 2014
    ..Moreover, we have identified leucine rich repeat kinase 2 (LRRK2) as a novel kinase involved in microglial proinflammatory responses and phagocytosis in response to HIV-1 Tat...
  17. MECHANISMS OF NEURONAL DEATH IN PARKINSON'S DISEASE
    KAREN L OMALLEY; Fiscal Year: 2012
    ..that this occurs via mitochondrial-dependent and independent processes, and that mutations in the PD-linked gene LRRK2 will affect similar transport processes of organelles and vesicles as MPP+...
  18. Beate R Ritz; Fiscal Year: 2015
    ..interactions for recognized PD risk genes (PARK1/PARK4 SNCA, PARK2 parkin, PARK5 UCHL1, PARK6 PINK, PARK8 LRRK2, and PARK13 HTRA2)...
  19. Zhenyu Yue; Fiscal Year: 2015
    ..approach, we have previously investigated normal and pathophysiological functions of Leucine-rich-repeat-kinase 2 (LRRK2), a newly identified causative gene for familial PD, in mouse models...
  20. LRRK2 and Neurodegeneration
    Benjamin L Wolozin; Fiscal Year: 2013
    Mutations in LRRK2 are a common genetic cause of Parkinson's disease (PD). Diseases associated with LRRK2 are associated with both alpha-synuclein pathology and with tau pathology...
  21. Biomarkers for Preclinical Parkinson's disease
    Jing Zhang; Fiscal Year: 2012
    ..e. a nonhuman primate treated with MPTP and familial PD patients secondary to LRRK2 mutations...
  22. Mark S Moehle; Fiscal Year: 2014
    DESCRIPTION (provided by applicant): Missense mutations in LRRK2 account for between 1 and 5% of late onset PD cases in most Caucasian populations...
  23. Biophysical analysis of LRRK2
    DAVID MICHAEL JAMESON; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Mutations in the gene for Leucine-Rich Repeat Kinase 2 (LRRK2) are responsible for an autosomal dominant form of Parkinson's Disease (PD)...
  24. Jie Shen; Fiscal Year: 2014
    ..sporadic PD have been linked to mutations in at least 5 distinct genes (1-synuclein, parkin, DJ-1, PINK1 and LRRK2)...
  25. Robert E Burke; Fiscal Year: 2014
    ..Projects 2 (Dauer) and 3 (Greene) will explore, in collaboration, mechanisms of LRRK2 toxicity...
  26. Confocal Microscope for the Study of Neurologic Diseases
    Tracy L Young-Pearse; Fiscal Year: 2012
    ..Similarly, mutations in genes such as alpha-synuclein, PINK1, LRRK2, and Parkin are linked to PD and their study in our disease models also benefits greatly from the use of the ..
  27. LRRK2 and RhoGTPases: Local translation in neurodegeneration
    Diane Chan; Fiscal Year: 2012
    ..causes of Parksinson's disease reveal that mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) is the most common cause of familial PD...
  28. Regulation of Leucine Rich Repeat Kinase 2 (LRRK2)
    Matthew J LaVoie; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Missense mutations within the multi-domain kinase, LRRK2, are the most common cause of familial Parkinson's disease (PD), accounting for up to 40% of cases in some populations...
  29. Parkinson's Disease Mouse Model with Mutant LRRK2
    Christopher A Ross; Fiscal Year: 2011
    ..b>LRRK2 mutations constitute the most common identified cause of human PD, accounting for up to 20% of PD in some ..
  30. LRRK2 modulates the progression of neuropathology in a mouse model of tauopathy
    Rachel M Bailey; Fiscal Year: 2013
    ..In view of this, it is interesting that mutations in the gene encoding Leucine-rich repeat kinase 2 (LRRK2), which are a major risk factor for PD, have been associated with pathologies that include tau tangles and ..
  31. Andrew B West; Fiscal Year: 2015
    ..We have made the recent observation that LRRK2, and other proteins linked genetically and pathologically to PD, are detectable in exosomes isolated from human ..
  32. Small Molecule Probes for Elucidating LRRK2 Kinase Functions
    Marcie A Glicksman; Fiscal Year: 2012
    ..However, recent studies have identified mutations in the leucine-rich repeat kinase2 gene (LRRK2) in the most common familial forms and some sporadic forms of Parkinson's disease (PD)...
  33. Ted M Dawson; Fiscal Year: 2016
    The overall goals of this proposal are to understand the role of a-synuclein, parkin, LRRK2 and the relationship with oxidative stress in the pathogenesis and pathology of Parkinson's disease (PD) and to define the molecular ..
  34. Jie Shen; Fiscal Year: 2014
    ..sporadic PD have been linked to mutations in at least 5 distinct genes (a-synuclein, parkin, DJ-1, PINK1 and LRRK2)...
  35. LRRK2 and Parkinson's Disease Cell Biology
    Christopher A Ross; Fiscal Year: 2011
    DESCRIPTION (provided by applicant): LRRK2 and Parkinson's disease cell biology Parkinson's disease is a disorder of movement, cognition and emotion, characterized neuropathologically by neuronal degeneration and deposits of ..
  36. Zhenyu Yue; Fiscal Year: 2016
    ..of this renewal R01 is to advance our understanding of the biology and pathology of Leucine-Rich Repeat Kinase 2 (LRRK2), whose mutations are the most common genetic cause of Parkinson's disease (PD)...
  37. Ole Isacson; Fiscal Year: 2014
    ..We and others have shown that cells from Parkinson's disease patients carrying LRRK2 or PINK1 mutations demonstrate mitochondrial deficits...
  38. PD iPS Cell Line Consortium
    Ole Isacson; Fiscal Year: 2013
    ..led by Zbigniew Wszoiek that will provide necessary patient fibroblast lines, including GBA, FTD and additional LRRK2 and alpha synuclein mutations, along with a mRNA sequencing and expression laboratory...
  39. Michael K Lee; Fiscal Year: 2015
    ..Recently, mutations in LRRK2 gene were shown to cause late-onset FPD with variable penetrance and a-synuclein (a-Syn) pathology (a-..
  40. Investigating Genetic and Environmental Etiologies of Parkinson's Ds in Zebrafish
    JEFF MICHAEL BRONSTEIN; Fiscal Year: 2010
    ..PD- associated genes to be tested include alpha-synuclein and LRRK2. Toxins to be tested will include the ubiquitin-proteasome system (UPS) inhibitor epoxomicin, and pesticides ..
  41. Exploration of motor deficits and cognitive impairments in LRRK2 transgenic mice
    Zhenyu Yue; Fiscal Year: 2009
    ..function deficits and cognitive impairments in a series of BAC-mediated transgenic mice, which over-express mutant LRRK2 carrying Parkinson's disease (PD)-linked familial mutation...
  42. Regulation of GTPase activity of LRRK2 and its implication in Parkinson?s disease
    Yongjian Liu; Fiscal Year: 2009
    DESCRIPTION (provided by applicant): Leucine-rich repeat kinase 2 (LRRK2) is a newly identified gene whose mutations are associated with late onset pathogenesis of Parkinson's disease (PD) and have unprecedented prevalence in both ..
  43. Using gene targeting to address the role of LRRK2 in Parkinson's disease
    Bruce Hostager; Fiscal Year: 2007
    ..As proof of principle, we will disrupt the gene encoding dardarin in a neuronal cell line...
  44. The Role of LRRK2 in the Pathogenesis of Parkinson's Disease
    Andrew B West; Fiscal Year: 2010
    ..genetic component to disease was recently identified as mutations in the leucirierich repeat kinase 2 gene (LRRK2). LRRK2 mutations cause a highly-penetrant dominant disease phenotype indistinguishable from typical PD...
  45. The Role of LRRK2 in the Pathogenesis of Parkinson's Disease
    Andrew West; Fiscal Year: 2007
    ..genetic component to disease was recently identified as mutations in the leucine- rich repeat kinase 2 gene (LRRK2). LRRK2 mutations cause a highly-penetrant dominant disease phenotype indistinguishable from typical PD...
  46. Structure-Activity Analysis of LRRK2 Associated:PD
    Shu Chen; Fiscal Year: 2007
    ..DESCRIPTION (provided by applicant): Mutations in a novel gene encoding the leucine-rich repeat kinase 2 (LRRK2) have recently been shown to be the most common cause of autosomal dominant, late-onset Parkinson's disease...
  47. Analyzing the function of the Parkinson's Disease gene dardarin using Drosophila.
    Mark W Dodson; Fiscal Year: 2010
    ..b>dardarin (dar), the most recently identified PD gene, encodes a large protein belonging to a novel protein family with Ras/..
  48. Molecular Regulation and Celluar Signaling of Lrrk2 in Parkinson's Disease
    Kathleen Gallo; Fiscal Year: 2007
    ..Mutations in the Leucine rich repeat kinase 2 (Lrrk2) are associated with an autosomal dominant form of Parkinson's...
  49. DBH as a Modifying Gene in Neurodegenerative Diseases
    Cyrus Zabetian; Fiscal Year: 2006
    ..Comparing plasma and tissue levels of DBH protein and catecholamines in the two lines will detect the effect of each allele on DBH expression. ..
  50. CLONING OF FAMILIAL PRIMARY PULMONARY HYPERTENSION GENE
    William Nichols; Fiscal Year: 2006
    ..abstract_text> ..
  51. LRRK2 Proteomics: Kinase/GTPase Hypothesis and Interaction Partners
    Zhenyu Yue; Fiscal Year: 2007
    ..Recent discovery of mutations of LRRK2 which cause familial PD presents an opportunity to identify such cellular mechanisms or pathways...
  52. Reversible and Temporally Inducible LRRK2 Knockout Mice
    Ted Dawson; Fiscal Year: 2007
    unreadable] DESCRIPTION (provided by applicant): Mutations in the LRRK2/Dardarin gene are a common cause of autosomal dominant Parkinson's disease (PD)...
  53. Models of Familial Parkinson's Disease: DJ-1 Knockouts
    Ted Dawson; Fiscal Year: 2005
    ....
  54. Apoptosis Inducing Factor in Dopaminergic Cell Death
    Ted Dawson; Fiscal Year: 2003
    ....
  55. Models of Familial Parkinson's Disease: PINK1
    Ted Dawson; Fiscal Year: 2006
    ....
  56. The Role of Parkin in Parkinson's Disease
    Ted Dawson; Fiscal Year: 2009
    ....
  57. Beta-glucocerebrosidase Mutations and PD in the Ashkenazim
    Lorraine Clark; Fiscal Year: 2006
    ..Significantly, recent studies suggest that mutations in the GBA gene may be associated with Parkinson's disease and the lysosomal/autophagic pathway has also been implicated in PD pathogenesis. [unreadable] [unreadable]..
  58. Divalent Metal Transporter: Role in Manganese Toxicity
    JEROME ROTH; Fiscal Year: 2004
    ....
  59. Regulation of PTEN-induced kinase 1 (PINK 1)
    Charleen Chu; Fiscal Year: 2007
    ..In addition, a group of immunochemical and molecular reagents will have been created that can facilitate the work of other investigators studying mechanisms of Parkinson's and related diseases. [unreadable] [unreadable]..
  60. Interaction Between Genes and the Mitochondria in Parkin
    Benjamin L Wolozin; Fiscal Year: 2010
    ..Aim 3 will determine whether combined use of a mitochondrial complex II stimulant plus an apoptotic inhibitor or antioxidant protects neurons against degeneration in transgenic mice carrying the A53T alpha-synuclein transgene.. ..
  61. Assays for rapid identification of Hsp70 modulators
    Gabriela Chiosis; Fiscal Year: 2008
    ..abstract_text> ..
  62. Isolation of Inhibitors of Her-Kinase Expression (RMI)
    Gabriela Chiosis; Fiscal Year: 2005
    ..To our knowledge, this has not been accomplished, and we believe that we are uniquely positioned to initiate this goal. ..
  63. Genetic Analysis of Familial Parkinson Disease Genes Pa
    Asa Abeliovich; Fiscal Year: 2003
    ..and Parkin mutations cause dopamine neuron loss? --Do mutations in alpha-Syn and Parkin act within a common genetic pathway? --How do the normal activities of these proteins relate to their pathological functions? ..
  64. Molecular and Cellular Mechanisms of Primary Dystonia
    William Dauer; Fiscal Year: 2007
    ..We believe that the results of the work may provide insight into the neurobiology of dystonia and suggest rational avenues for exploring therapy for the disease. [unreadable] [unreadable]..
  65. Mapping a Gene for Parkinsons Disease in Norway
    Matthew Farrer; Fiscal Year: 2005
    ..We will explore the utility of haplotype tagging (htSNPs) to capture disease-association (Aim 3). Identification of the PD-susceptibility gene will be confirmed in US samples and functionally assessed. ..
  66. Ubiquitination/Receptor Signaling--Regulation by Parkin
    Benjamin Wolozin; Fiscal Year: 2004
    ..abstract_text> ..
  67. Molecular and Cellular Analysis of DJ-1 Function
    Asa Abeliovich; Fiscal Year: 2009
    ..We propose to investigate the mechanism of DJ-1 activity using complementary biochemical, cellular, and mouse genetic approaches. ..
  68. Mouse Models And LRRK2 Kinase Substrates for Park8-Parkinson's Disease
    Chenjian Li; Fiscal Year: 2007
    unreadable] DESCRIPTION (provided by applicant): The newly identified LRRK2, a disease gene of familial dominant late-onset ParkS, encodes a kinase...
  69. LRRK2 and cellular pathways of Parkinson's Disease
    Wanli Smith; Fiscal Year: 2007
    ..Mutations in LRRK2 (or dardarin) have been recently identified to cause autosomal dominant late onset, clinically typical PD with pleomorphic ..
  70. Genetic Analysis of Tau H1 in Parkinsonism
    Matthew Farrer; Fiscal Year: 2006
    ..abstract_text> ..
  71. PROSTAGLANDIN E2 RECEPTORS IN GASTROINTESTINAL INJURY
    Courtney Houchen; Fiscal Year: 2004
    ....
  72. Axonal Degeneration in LRRK2 Parkinson?s Disease
    Chenjian Li; Fiscal Year: 2010
    ..Mutations in Leucine-rich-repeat-kinase 2 (LRRK2), the newly identified causative gene for PARK8 type PD with autosomal dominant inheritance, are the most ..
  73. The Mechanism of LRRK2-Mediated Neurodegneration in Parkinson's Disease
    William T Dauer; Fiscal Year: 2010
    ..aim of this application is to develop insight into the molecular pathways that underlie PD through studies of LRRK2 (leucine-rich repeat kinase 2), the most common genetic cause of the disease...
  74. Alpha-Synuclein Conditional Knock-in Mice as Novel Models of Parkinson's Disease
    Darren Moore; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  75. Training in proteomics of novel kinase substrates for neurodegeneration
    Charleen Chu; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable] [unreadable] [unreadable]..
  76. Molecular and Cellular Analyses of Parkin Function
    Asa Abeliovich; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  77. MOLECULAR MECHANISMS OF THE PARKINSON'S DISEASE GENES
    Asa Abeliovich; Fiscal Year: 2007
    ..Of particular interest are potential relationships among these molecules. I propose to combine complementary biochemical, cellular, and genetic approaches to this end. ..
  78. Regulation of APP Processing by Presenilins
    Benjamin Wolozin; Fiscal Year: 2004
    ..Identification of mutant forms of presenilin that inhibit beta- amyloid production could lead to novel strategies for therapeutic intervention in Alzheimer's disease. ..