Lrrk2

Summary

Gene Symbol: Lrrk2
Description: leucine-rich repeat kinase 2
Alias: 4921513O20Rik, 9330188B09Rik, AW561911, D630001M17Rik, Gm927, cI-46, leucine-rich repeat serine/threonine-protein kinase 2
Species: mouse

Top Publications

  1. pmc Leucine-rich repeat kinase 2 (LRRK2)/PARK8 possesses GTPase activity that is altered in familial Parkinson's disease R1441C/G mutants
    Xianting Li
    Departments of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, USA
    J Neurochem 103:238-47. 2007
  2. pmc Substrate specificity and inhibitors of LRRK2, a protein kinase mutated in Parkinson's disease
    R Jeremy Nichols
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 424:47-60. 2009
  3. 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
  4. pmc LRRK2 protein levels are determined by kinase function and are crucial for kidney and lung homeostasis in mice
    Martin C Herzig
    Department of Neuroscience, Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH 4002 Basel, Switzerland
    Hum Mol Genet 20:4209-23. 2011
  5. 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
  6. pmc Leucine-rich repeat kinase 2 regulates the progression of neuropathology induced by Parkinson's-disease-related mutant alpha-synuclein
    Xian Lin
    Unit of Transgenesis, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA
    Neuron 64:807-27. 2009
  7. pmc Loss of leucine-rich repeat kinase 2 causes impairment of protein degradation pathways, accumulation of alpha-synuclein, and apoptotic cell death in aged mice
    Youren Tong
    Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 107:9879-84. 2010
  8. pmc Inhibition of LRRK2 kinase activity leads to dephosphorylation of Ser(910)/Ser(935), disruption of 14-3-3 binding and altered cytoplasmic localization
    Nicolas Dzamko
    University of Dundee, Scotland, UK
    Biochem J 430:405-13. 2010
  9. 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
  10. 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

Scientific Experts

  • H L Melrose
  • Marie Paus
  • Youren Tong
  • Patrick A Lewis
  • Zhenyu Yue
  • B Winner
  • R Jeremy Nichols
  • Saskia Biskup
  • Frank Gillardon
  • Wanli W Smith
  • Min Liu
  • Ted M Dawson
  • Valina L Dawson
  • Darren J Moore
  • Xianting Li
  • Huaibin Cai
  • Loukia Parisiadou
  • Jean Marc Taymans
  • Martin C Herzig
  • Andrew B West
  • Veerle Baekelandt
  • Lixin Sun
  • Chengsong Xie
  • Xian Lin
  • Dagmar Galter
  • Philip J Webber
  • Klodjan Stafa
  • Alzbeta Trancikova
  • Hyun Jin Cho
  • Juan C Troncoso
  • Yulan Xiong
  • Evy Lobbestael
  • Jinhui Ding
  • Andrea Meixner
  • Mark R Cookson
  • Marius Ueffing
  • Zhihua Liu
  • Tatsunori Maekawa
  • Xiaodong Ding
  • Makoto Kubo
  • Xiaojie Li
  • Han Seok Ko
  • Lizhen Wang
  • Marie Westerlund
  • Taku Hatano
  • Mareike Caesar
  • Patrícia Silva Guerreiro
  • Renee Vancraenenbroeck
  • Zejuan Sheng
  • Laura Civiero
  • Wim Mandemakers
  • Daniel C Berwick
  • Iakov N Rudenko
  • Liliane Glauser
  • Nicholas G James
  • C Y Chen
  • Mark S Moehle
  • João Paulo L Daher
  • Beomsue Kim
  • Jingwen Niu
  • Giorgio Rovelli
  • Christine Stemmelen
  • Tatjana Schweizer
  • Thomas Hafner
  • Peter Schmid
  • Derya R Shimshek
  • Simone Danner
  • P Herman van der Putten
  • Matthias Bauer
  • Giovanni Piccoli
  • Karsten Boldt
  • Cathrin Schulz
  • Yiyuan Yuan
  • Christian Johannes Gloeckner
  • Matthew S Goldberg
  • Fumiya Obata
  • Karina Haebig
  • Etsuro Ohta
  • Elisa Greggio
  • Nicolas Dzamko
  • Sabrina Zechel
  • Justus C Dachsel
  • Wongi Seol
  • Byoung Dae Lee
  • Leonard Petrucelli
  • Joo Ho Shin
  • Yun Il Lee
  • Cherry Cheng Ying Ho
  • Eva Andres-Mateos
  • Cai Xia Long

Detail Information

Publications66

  1. pmc Leucine-rich repeat kinase 2 (LRRK2)/PARK8 possesses GTPase activity that is altered in familial Parkinson's disease R1441C/G mutants
    Xianting Li
    Departments of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, USA
    J Neurochem 103:238-47. 2007
    Mutations in Leucine-rich repeat kinase 2 (LRRK2) are linked to the most common familial forms and some sporadic forms of Parkinson's disease (PD)...
  2. pmc Substrate specificity and inhibitors of LRRK2, a protein kinase mutated in Parkinson's disease
    R Jeremy Nichols
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 424:47-60. 2009
    The LRRK2 (leucine-rich repeat protein kinase-2) is mutated in a significant number of Parkinson's disease patients, but little is known about its regulation and function...
  3. 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)...
  4. pmc LRRK2 protein levels are determined by kinase function and are crucial for kidney and lung homeostasis in mice
    Martin C Herzig
    Department of Neuroscience, Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH 4002 Basel, Switzerland
    Hum Mol Genet 20:4209-23. 2011
    Mutations in leucine-rich repeat kinase 2 (LRRK2) cause late-onset Parkinson's disease (PD), but the underlying pathophysiological mechanisms and the normal function of this large multidomain protein remain speculative...
  5. 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...
  6. pmc Leucine-rich repeat kinase 2 regulates the progression of neuropathology induced by Parkinson's-disease-related mutant alpha-synuclein
    Xian Lin
    Unit of Transgenesis, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA
    Neuron 64:807-27. 2009
    Mutations in alpha-synuclein and Leucine-rich repeat kinase 2 (LRRK2) are linked to autosomal dominant forms of Parkinson's disease (PD)...
  7. pmc Loss of leucine-rich repeat kinase 2 causes impairment of protein degradation pathways, accumulation of alpha-synuclein, and apoptotic cell death in aged mice
    Youren Tong
    Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 107:9879-84. 2010
    Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease. LRRK2 is a large protein containing a small GTPase domain and a kinase domain, but its physiological role is unknown...
  8. pmc Inhibition of LRRK2 kinase activity leads to dephosphorylation of Ser(910)/Ser(935), disruption of 14-3-3 binding and altered cytoplasmic localization
    Nicolas Dzamko
    University of Dundee, Scotland, UK
    Biochem J 430:405-13. 2010
    b>LRRK2 (leucine-rich repeat protein kinase 2) is mutated in a significant number of Parkinson's disease patients...
  9. 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...
  10. 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)...
  11. 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...
  12. 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...
  13. ncbi The familial Parkinsonism gene LRRK2 regulates neurite process morphology
    David Macleod
    Departments of Pathology and Neurology, Center for Neurobiology and Behavior and Taub Institute, Columbia University, College of Physicians and Surgeons 15 403, 630 West 168th Street, New York, New York 10032, USA
    Neuron 52:587-93. 2006
    Mutations in LRRK2 underlie an autosomal-dominant, inherited form of Parkinson's disease (PD) that mimics the clinical features of the common "sporadic" form of PD...
  14. ncbi Expression and localization of Parkinson's disease-associated leucine-rich repeat kinase 2 in the mouse brain
    Shinji Higashi
    Laboratory of Molecular Neuroscience, The Babraham Institute, Babraham, Cambridge, UK
    J Neurochem 100:368-81. 2007
    Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) have been identified as the cause of familial Parkinson's disease (PD) at the PARK8 locus...
  15. ncbi Anatomical localization of leucine-rich repeat kinase 2 in mouse brain
    H Melrose
    Department of Neuroscience, Genetics of Parkinsonism and Related Disorders, Morris K Udall Parkinson s Disease Research Center of Excellence, Birdsall Building, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Neuroscience 139:791-4. 2006
    Mutations in leucine-rich repeat kinase 2 (LRRK2) have recently been identified in autosomal dominant late-onset Parkinson's disease...
  16. doi LRRK2 and human disease: a complicated question or a question of complexes?
    Patrick A Lewis
    Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
    Sci Signal 5:pe2. 2012
    Leucine-rich repeat kinase 2 (LRRK2) is linked to various diseases, including Parkinson's disease, cancer, and leprosy...
  17. pmc Loss of leucine-rich repeat kinase 2 causes age-dependent bi-phasic alterations of the autophagy pathway
    Youren Tong
    Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA
    Mol Neurodegener 7:2. 2012
    Dominantly inherited missense mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease, but its normal physiological function remains unclear...
  18. 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)...
  19. ncbi Distribution of PINK1 and LRRK2 in rat and mouse brain
    Jean Marc Taymans
    Laboratory for Neurobiology and Gene Therapy, Division of Molecular Medicine Katholieke Universiteit Leuven, Leuven, Belgium
    J Neurochem 98:951-61. 2006
    Mutations in two kinases, PTEN induced kinase 1 (PINK1) and leucine-rich repeat kinase 2 (LRRK2), have been shown to segregate with familial forms of Parkinson's disease...
  20. pmc A QUICK screen for Lrrk2 interaction partners--leucine-rich repeat kinase 2 is involved in actin cytoskeleton dynamics
    Andrea Meixner
    Department of Protein Science, Helmholtz Zentrum Munchen German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany
    Mol Cell Proteomics 10:M110.001172. 2011
    Mutations in human leucine-rich repeat kinase 2 (Lrrk2), a protein of yet unknown function, are linked to Parkinson's disease caused by degeneration of midbrain dopaminergic neurons...
  21. doi LRRK2 is expressed in B-2 but not in B-1 B cells, and downregulated by cellular activation
    Makoto Kubo
    Division of Clinical Immunology, Graduate School of Medical Sciences, Kitasato University, Minami Ku, Sagamihara, Kanagawa, Japan
    J Neuroimmunol 229:123-8. 2010
    b>LRRK2, the causal molecule of familial Parkinson's disease, is expressed strongly by one of the B cell subsets, B-2 cells, but not by the other subset, B-1 cells, in the mouse peritoneal cavity, spleen, and peripheral blood...
  22. doi Lrrk2 and alpha-synuclein are co-regulated in rodent striatum
    Marie Westerlund
    Department of Neuroscience, Karolinska Institutet, Retzius väg 8 B2 4, S 17177 Stockholm, Sweden
    Mol Cell Neurosci 39:586-91. 2008
    b>LRRK2, alpha-synuclein, UCH-L1 and DJ-1 are implicated in the etiology of Parkinson's disease...
  23. pmc Phosphorylation-dependent 14-3-3 binding to LRRK2 is impaired by common mutations of familial Parkinson's disease
    Xianting Li
    Department of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, New York, United States of America
    PLoS ONE 6:e17153. 2011
    Recent studies show that mutations in Leucine Rich Repeat Kinase 2 (LRRK2) are the cause of the most common inherited and some sporadic forms of Parkinson's disease (PD)...
  24. pmc Phosphorylation of ezrin/radixin/moesin proteins by LRRK2 promotes the rearrangement of actin cytoskeleton in neuronal morphogenesis
    Loukia Parisiadou
    Unit of Transgenesis, Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD 20892, USA
    J Neurosci 29:13971-80. 2009
    Leucine-rich repeat kinase 2 (LRRK2) functions as a putative protein kinase of ezrin, radixin, and moesin (ERM) family proteins...
  25. pmc ARHGEF7 (Beta-PIX) acts as guanine nucleotide exchange factor for leucine-rich repeat kinase 2
    Karina Haebig
    Department of Medical Genetics, Institute of Human Genetics, University of Tuebingen, Tuebingen, Germany
    PLoS ONE 5:e13762. 2010
    Mutations within the leucine-rich repeat kinase 2 (LRRK2) gene are a common cause of familial and sporadic Parkinson's disease. The multidomain protein LRRK2 exhibits overall low GTPase and kinase activity in vitro.
  26. pmc Biochemical characterization of highly purified leucine-rich repeat kinases 1 and 2 demonstrates formation of homodimers
    Laura Civiero
    Department of Biology, University of Padova, Padova, Italy
    PLoS ONE 7:e43472. 2012
    Leucine-rich repeat kinase 1 and 2 (LRRK1 and LRRK2) are large multidomain proteins containing kinase, GTPase and multiple protein-protein interaction domains, but only mutations in LRRK2 are linked to familial Parkinson's disease (PD)...
  27. pmc GTPase activity and neuronal toxicity of Parkinson's disease-associated LRRK2 is regulated by ArfGAP1
    Klodjan Stafa
    Laboratory of Molecular Neurodegenerative Research, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Federale de Lausanne EPFL, Lausanne, Switzerland
    PLoS Genet 8:e1002526. 2012
    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of autosomal dominant familial Parkinson's disease (PD) and also contribute to idiopathic PD...
  28. pmc ArfGAP1 is a GTPase activating protein for LRRK2: reciprocal regulation of ArfGAP1 by LRRK2
    Yulan Xiong
    Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Neurosci 32:3877-86. 2012
    ..dominant forms of Parkinson's disease (PD) have been causally linked to mutations in leucine-rich repeat kinase 2 (LRRK2), a large protein with multiple domains. The kinase domain plays an important role in LRRK2-mediated toxicity...
  29. 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...
  30. pmc Dynamic and redundant regulation of LRRK2 and LRRK1 expression
    Saskia Biskup
    Institute for Cell Engineering and Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, USA
    BMC Neurosci 8:102. 2007
    Mutations within the leucine-rich repeat kinase 2 (LRRK2) gene account for a significant proportion of autosomal-dominant and some late-onset sporadic Parkinson's disease...
  31. ncbi LRRK2 is expressed in areas affected by Parkinson's disease in the adult mouse brain
    Javier Simon-Sanchez
    Unitat de Genetica Molecular, Departament de Genòmica i Proteòmica, Institut de Biomedicina de València CSIC, C Jaume Roig, 11, E46010 Valencia, Spain
    Eur J Neurosci 23:659-66. 2006
    The leucine-rich repeat kinase 2 (LRRK2) gene was recently found to have multiple mutations that are causative for autosomal dominant inherited Parkinson's disease (PD)...
  32. ncbi LRRK2 expression linked to dopamine-innervated areas
    Dagmar Galter
    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
    Ann Neurol 59:714-9. 2006
    Leucine-rich repeat kinase 2 (LRRK2) has been linked to Parkinson's disease. Our study explores the expression of LRRK2 in human and rodent brain tissue.
  33. pmc Enhanced striatal dopamine transmission and motor performance with LRRK2 overexpression in mice is eliminated by familial Parkinson's disease mutation G2019S
    Xianting Li
    Department of Neurology, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Neurosci 30:1788-97. 2010
    PARK8/LRRK2 (leucine-rich repeat kinase 2) was recently identified as a causative gene for autosomal dominant Parkinson's disease (PD), with LRRK2 mutation G2019S linked to the most frequent familial form of PD...
  34. pmc The Parkinson disease protein leucine-rich repeat kinase 2 transduces death signals via Fas-associated protein with death domain and caspase-8 in a cellular model of neurodegeneration
    Cherry Cheng Ying Ho
    Department of Pathology, Columbia University, New York, New York 10032, USA
    J Neurosci 29:1011-6. 2009
    ..Dominant missense mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson disease (PD), but the mechanisms by which mutant forms of LRRK2 ..
  35. pmc CHIP regulates leucine-rich repeat kinase-2 ubiquitination, degradation, and toxicity
    Han Seok Ko
    Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 106:2897-902. 2009
    Mutation in leucine-rich repeat kinase-2 (LRRK2) is the most common cause of late-onset Parkinson's disease (PD). Although most cases of PD are sporadic, some are inherited, including those caused by LRRK2 mutations...
  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. pmc R1441C mutation in LRRK2 impairs dopaminergic neurotransmission in mice
    Youren Tong
    Center for Neurologic Diseases, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 106:14622-7. 2009
    Dominantly inherited mutations in leucine-rich repeat kinase 2 (LRRK2) are a common genetic cause of Parkinson's disease (PD)...
  38. 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...
  39. pmc Unexpected lack of hypersensitivity in LRRK2 knock-out mice to MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
    Eva Andres-Mateos
    Neuroregeneration Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Neurosci 29:15846-50. 2009
    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common known cause of Parkinson's disease (PD)...
  40. doi Expression of leucine-rich-repeat-kinase 2 (LRRK2) during embryonic development
    Sabrina Zechel
    Interdisciplinary Center for Neurosciences IZN, Dept of Neuroanatomy, University of Heidelberg, Germany
    Int J Dev Neurosci 28:391-9. 2010
    The LRRK2 gene was recently found to have multiple mutations that are causative for the most common inherited form of late onset Parkinson's disease...
  41. pmc High LRRK2 levels fail to induce or exacerbate neuronal alpha-synucleinopathy in mouse brain
    Martin C Herzig
    Department of Neuroscience, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland
    PLoS ONE 7:e36581. 2012
    The G2019S mutation in the multidomain protein leucine-rich repeat kinase 2 (LRRK2) is one of the most frequently identified genetic causes of Parkinson's disease (PD)...
  42. 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...
  43. doi The G2385R variant of leucine-rich repeat kinase 2 associated with Parkinson's disease is a partial loss-of-function mutation
    Iakov N Rudenko
    Cell Biology and Gene Expression Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA
    Biochem J 446:99-111. 2012
    Autosomal-dominant missense mutations in LRRK2 (leucine-rich repeat kinase 2) are a common genetic cause of PD (Parkinson's disease). LRRK2 is a multidomain protein with kinase and GTPase activities...
  44. pmc Number and brightness analysis of LRRK2 oligomerization in live cells
    Nicholas G James
    Department of Cell and Molecular Biology, John A Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA
    Biophys J 102:L41-3. 2012
    Leucine-rich repeat kinase 2 (LRRK2) is a large multidomain protein that contains enzymatically functional GTPase and kinase domains...
  45. pmc LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6
    Daniel C Berwick
    Department of Pharmacology, UCL School of Pharmacy, University College London, 29 39 Brunswick Square, London, UK
    Hum Mol Genet 21:4966-79. 2012
    Mutations in PARK8, encoding leucine-rich repeat kinase 2 (LRRK2), are a frequent cause of Parkinson's disease (PD). Nonetheless, the physiological role of LRRK2 remains unclear...
  46. pmc MicroRNA-205 regulates the expression of Parkinson's disease-related leucine-rich repeat kinase 2 protein
    Hyun Jin Cho
    Transgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA
    Hum Mol Genet 22:608-20. 2013
    Recent genome-wide association studies indicate that a simple alteration of Leucine-rich repeat kinase 2 (LRRK2) gene expression may contribute to the etiology of sporadic Parkinson's disease (PD)...
  47. 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...
  48. doi Ser1292 autophosphorylation is an indicator of LRRK2 kinase activity and contributes to the cellular effects of PD mutations
    Zejuan Sheng
    Department of Neurosciences, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA
    Sci Transl Med 4:164ra161. 2012
    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of familial Parkinson's disease (PD)...
  49. ncbi Genetic analysis of Parkinson's disease-linked leucine-rich repeat kinase 2
    Youren Tong
    Center for Neurologic Diseases, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA 02115, U S A
    Biochem Soc Trans 40:1042-6. 2012
    Mutations in LRRK2 (leucine-rich repeat kinase 2) are the most common genetic cause of PD (Parkinson's disease)...
  50. pmc LRRK2 interactions with α-synuclein in Parkinson's disease brains and in cell models
    Patrícia Silva Guerreiro
    Cell and Molecular Neuroscience Unit, Instituto de Medicina Molecular, Lisbon 04250, Portugal
    J Mol Med (Berl) 91:513-22. 2013
    Mutations in the genes encoding leucine-rich repeat kinase 2 (LRRK2) and α-synuclein are associated with both autosomal dominant and idiopathic forms of Parkinson's disease (PD)...
  51. 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...
  52. pmc (G2019S) LRRK2 activates MKK4-JNK pathway and causes degeneration of SN dopaminergic neurons in a transgenic mouse model of PD
    C Y Chen
    Department of Physiology, Chang Gung University School of Medicine, Tao Yuan, Taiwan, ROC
    Cell Death Differ 19:1623-33. 2012
    G2019S) mutation of leucine-rich repeat kinase 2 (LRRK2) is the most common genetic cause of both familial and sporadic Parkinson's disease (PD) cases...
  53. pmc Impaired inflammatory responses in murine Lrrk2-knockdown brain microglia
    Beomsue Kim
    Department of Pharmacology, Ajou University School of Medicine, Suwon, Korea
    PLoS ONE 7:e34693. 2012
    b>LRRK2, a Parkinson's disease associated gene, is highly expressed in microglia in addition to neurons; however, its function in microglia has not been evaluated...
  54. pmc Neurodegenerative phenotypes in an A53T α-synuclein transgenic mouse model are independent of LRRK2
    João Paulo L Daher
    Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Hum Mol Genet 21:2420-31. 2012
    Mutations in the genes encoding LRRK2 and α-synuclein cause autosomal dominant forms of familial Parkinson's disease (PD)...
  55. 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...
  56. pmc Dysregulated LRRK2 signaling in response to endoplasmic reticulum stress leads to dopaminergic neuron degeneration in C. elegans
    Yiyuan Yuan
    Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America
    PLoS ONE 6:e22354. 2011
    Mutation of leucine-rich repeat kinase 2 (LRRK2) is the leading genetic cause of Parkinson's Disease (PD), manifested as age-dependent dopaminergic neurodegeneration, but the underlying molecular mechanisms remain unclear...
  57. doi LRRK2 expression is enriched in the striosomal compartment of mouse striatum
    Wim Mandemakers
    Center for Human Genetics, K U Leuven, Belgium
    Neurobiol Dis 48:582-93. 2012
    In spite of a clear genetic link between Parkinson's disease (PD) and mutations in LRRK2, cellular localization and physiological function of LRRK2 remain debated...
  58. ncbi Identification of cAMP analogue inducible genes in RAW264 macrophages
    Y Takahashi
    Laboratory of Biochemical Genetics and Metabolism, Box 179, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Biochim Biophys Acta 1492:385-94. 2000
    ..ABC1 was upregulated in RAW cells by cAMP, concurrent with the cAMP induction of lipid efflux to apolipoprotein A1...
  59. pmc Regulation of LRRK2 stability by the E3 ubiquitin ligase CHIP
    Xiaodong Ding
    Department of Neurology, The University of Texas Southwestern Medical Center, Dallas, Texas, United States of America
    PLoS ONE 4:e5949. 2009
    Dominantly inherited mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are the most common cause of familial Parkinson's disease (PD) and have also been identified in individuals with sporadic PD...
  60. pmc Kinetic mechanistic studies of wild-type leucine-rich repeat kinase 2: characterization of the kinase and GTPase activities
    Min Liu
    Laboratory for Drug Discovery in Neurodegeneration, Harvard NeuroDiscovery Center, 65 Landsdowne Street, Fourth Floor, Cambridge, Massachusetts 02139, USA
    Biochemistry 49:2008-17. 2010
    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)...
  61. pmc A comparative study of Lrrk2 function in primary neuronal cultures
    Justus C Dachsel
    Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA
    Parkinsonism Relat Disord 16:650-5. 2010
    To assess the contribution of wild-type, mutant and loss of leucine-rich repeat kinase-2 (LRRK2; Lrrk2) on dendritic neuronal arborization.
  62. pmc Adult neurogenesis and neurite outgrowth are impaired in LRRK2 G2019S mice
    B Winner
    Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92186, USA
    Neurobiol Dis 41:706-16. 2011
    ..In autosomal dominant PD, mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are frequent...
  63. pmc Leucine-rich repeat kinase 2 modulates retinoic acid-induced neuronal differentiation of murine embryonic stem cells
    Cathrin Schulz
    Boehringer Ingelheim Pharma GmbH and Co KG, CNS Research, Biberach an der Riss, Germany
    PLoS ONE 6:e20820. 2011
    Dominant mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most prevalent cause of Parkinson's disease, however, little is known about the biological function of LRRK2 protein...
  64. doi Age-dependent and cell-population-restricted LRRK2 expression in normal mouse spleen
    Tatsunori Maekawa
    Division of Clinical Immunology, Kitasato University, 1 15 1 Kitasato, Kanagawa 228 8555, Japan
    Biochem Biophys Res Commun 392:431-5. 2010
    Leucine-rich repeat kinase 2 (LRRK2) is the causal molecule of familial Parkinson's disease (PD), but its true physiological function remains unknown...
  65. doi The kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel disease
    Zhihua Liu
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland, USA
    Nat Immunol 12:1063-70. 2011
    Leucine-rich repeat kinase 2 (LRRK2) has been identified by genome-wide association studies as being encoded by a major susceptibility gene for Crohn's disease...
  66. doi LRRK2 and neurodegeneration
    Gabriel Santpere
    Institut de Neuropatologia, IDIBELL Hospital Universitari de Bellvitge, Universitat de Barcelona, Hospitalet de Llobregat, CIBERNED, Barcelona, Spain
    Acta Neuropathol 117:227-46. 2009
    Mutations in leucine-rich repeat kinase 2 gene (PARK8/LRRK2) encoding the protein Lrrk2 are causative of inherited and sporadic Parkinson's disease (PD) with phenotypic manifestations of frontotemporal lobar degeneration, corticobasal ..

Research Grants10

  1. LRRK2 and cellular pathways of Parkinson's Disease
    Wanli Smith; Fiscal Year: 2007
    ..Five major genetic causes have been identified, including mutations in alpha-synuclein, parkin, PINK1, DJ-1 and LRRK2, and these mutations have provided models for study of the pathogenesis of genetic PD, with implications for ..
  2. Using BAC-transgenic and Proteomic Approach to Study LRRK2 Biology and Pathology
    Zhenyu Yue; Fiscal Year: 2010
    The disease mechanism underlying Parkinson's disease (PD) is poorly understood. Mutations in LRRK2 (PARK8) have recently been linked to the most common familial forms (autosomal dominant) as well as some sporadic forms of Parkinson&..
  3. Neuronal Autophagy: a Cell-Autonomous Protection Mechanism
    Zhenyu Yue; Fiscal Year: 2010
    ..We will investigate how dysfunctional autophagy is connected to the pathological process in Parkinson's disease and further evaluate autophagy as drug target for the treatment of Parkinson's disease. ..
  4. Using BAC-transgenic and Proteomic Approach to Study LRRK2 Biology and Pathology
    Zhenyu Yue; Fiscal Year: 2010
    The disease mechanism underlying Parkinson's disease (PD) is poorly understood. Mutations in LRRK2 (PARK8) have recently been linked to the most common familial forms (autosomal dominant) as well as some sporadic forms of ..
  5. Neuronal Autophagy: a Cell-Autonomous Protection Mechanism
    Zhenyu Yue; Fiscal Year: 2009
    ..We will investigate how dysfunctional autophagy is connected to the pathological process in Parkinson's disease and further evaluate autophagy as drug target for the treatment of Parkinson's disease. ..
  6. 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...