Heterogeneity of Leucine-Rich Repeat Kinase 2 Mutations: Genetics, Mechanisms and Therapeutic Implications

Ribosomal Protein s15 Phosphorylation Mediates LRRK2 Neurodegeneration in Parkinson’s Disease

(2014) Ian Martin et al.   CELL

The Parkinson Disease-linked LRRK2 Protein Mutation I2020T Stabilizes an Active State Conformation Leading to Increased Kinase Activity

(2014) Soumya Ray et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Mutant LRRK2 Toxicity in Neurons Depends on LRRK2 Levels and Synuclein But Not Kinase Activity or Inclusion Bodies

(2014) G. Skibinski et al.   JOURNAL OF NEUROSCIENCE

LRRK2 regulates synaptogenesis and dopamine receptor activation through modulation of PKA activity

(2014) Loukia Parisiadou et al.   NATURE NEUROSCIENCE

Parkinson disease-associated mutation R1441H in LRRK2 prolongs the "active state" of its GTPase domain

(2014) J. Liao et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease

(2014) A. Beilina et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Pathogenic Parkinson’s disease mutations across the functional domains of LRRK2 alter the autophagic/lysosomal response to starvation

(2013) Claudia Manzoni et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Identification of protein phosphatase 1 as a regulator of the LRRK2 phosphorylation cycle

(2013) Evy Lobbestael et al.   BIOCHEMICAL JOURNAL

Differential Effects of Familial Parkinson Mutations in LRRK2 Revealed by a Systematic Analysis of Autophosphorylation

(2013) Shogo Kamikawaji et al.   BIOCHEMISTRY

Type II Kinase Inhibitors Show an Unexpected Inhibition Mode against Parkinson’s Disease-Linked LRRK2 Mutant G2019S

(2013) Min Liu et al.   BIOCHEMISTRY

Discovery of novel indolinone-based, potent, selective and brain penetrant inhibitors of LRRK2

(2013) Thomas Troxler et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

A Direct Interaction between Leucine-rich Repeat Kinase 2 and Specific β-Tubulin Isoforms Regulates Tubulin Acetylation

(2013) Bernard M. H. Law et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The genetics of Parkinson's disease: Progress and therapeutic implications

(2013) Andrew B. Singleton et al.   MOVEMENT DISORDERS

Leucine-rich repeat kinase 2 functionally interacts with microtubules and kinase-dependently modulates cell migration

(2013) Mareike Caesar et al.   NEUROBIOLOGY OF DISEASE

LRRK2 mutations cause mitochondrial DNA damage in iPSC-derived neural cells from Parkinson's disease patients: Reversal by gene correction

(2013) Laurie H. Sanders et al.   NEUROBIOLOGY OF DISEASE

RAB7L1 Interacts with LRRK2 to Modify Intraneuronal Protein Sorting and Parkinson’s Disease Risk

(2013) David A. MacLeod et al.   NEURON

Diapocynin prevents early Parkinson's disease symptoms in the leucine-rich repeat kinase 2 (LRRK2R1441G) transgenic mouse

(2013) Brian P. Dranka et al.   NEUROSCIENCE LETTERS

Comprehensive LRRK2 and GBA screening in Portuguese patients with Parkinson's disease: Identification of a new family with the LRRK2 p.Arg1441His mutation and novel missense variants

(2013) Lei Zhang et al.   PARKINSONISM & RELATED DISORDERS

Monogenic Parkinson's disease and parkinsonism: Clinical phenotypes and frequencies of known mutations

(2013) Andreas Puschmann   PARKINSONISM & RELATED DISORDERS

Small Molecule Kinase Inhibitors for LRRK2 and Their Application to Parkinson's Disease Models

(2012) Thomas Kramer et al.   ACS Chemical Neuroscience

The G2385R variant of leucine-rich repeat kinase 2 associated with Parkinson's disease is a partial loss-of-function mutation

(2012) Iakov N. Rudenko et al.   BIOCHEMICAL JOURNAL

The GTPase function of LRRK2

(2012) Jean-Marc Taymans   BIOCHEMICAL SOCIETY TRANSACTIONS

Is inhibition of kinase activity the only therapeutic strategy for LRRK2-associated Parkinson's disease?

(2012) Iakov N Rudenko et al.   BMC Medicine

(G2019S) LRRK2 activates MKK4-JNK pathway and causes degeneration of SN dopaminergic neurons in a transgenic mouse model of PD

(2012) C-Y Chen et al.   CELL DEATH AND DIFFERENTIATION

The LRRK2 G2019S mutant exacerbates basal autophagy through activation of the MEK/ERK pathway

(2012) José M. Bravo-San Pedro et al.   CELLULAR AND MOLECULAR LIFE SCIENCES

Kinases as Targets for Parkinson's Disease: From Genetics to Therapy

(2012) Renee Vancraenenbroeck et al.   CNS & Neurological Disorders-Drug Targets

Mechanisms of LRRK2-Mediated Neurodegeneration

(2012) Elpida Tsika et al.   Current Neurology and Neuroscience Reports

GTPase activity regulates kinase activity and cellular phenotypes of Parkinson's disease-associated LRRK2

(2012) A. Biosa et al.   HUMAN MOLECULAR GENETICS

LRRK2 regulates mitochondrial dynamics and function through direct interaction with DLP1

(2012) X. Wang et al.   HUMAN MOLECULAR GENETICS

Deep sequencing of theLRRK2gene in 14,002 individuals reveals evidence of purifying selection and independent origin of the p.Arg1628Pro mutation in Europe

(2012) Justin P. Rubio et al.   HUMAN MUTATION

Discovery of Highly Potent, Selective, and Brain-Penetrable Leucine-Rich Repeat Kinase 2 (LRRK2) Small Molecule Inhibitors

(2012) Anthony A. Estrada et al.   JOURNAL OF MEDICINAL CHEMISTRY

Leucine-rich repeat kinase 2 disturbs mitochondrial dynamics via Dynamin-like protein

(2012) Jingwen Niu et al.   JOURNAL OF NEUROCHEMISTRY

ArfGAP1 Is a GTPase Activating Protein for LRRK2: Reciprocal Regulation of ArfGAP1 by LRRK2

(2012) Y. Xiong et al.   JOURNAL OF NEUROSCIENCE

The I2020T Leucine-rich repeat kinase 2 transgenic mouse exhibits impaired locomotive ability accompanied by dopaminergic neuron abnormalities

(2012) Tatsunori Maekawa et al.   Molecular Neurodegeneration

LRRK2 Controls an EndoA Phosphorylation Cycle in Synaptic Endocytosis

(2012) Samer Matta et al.   NEURON

LRRK2 I2020T mutation is associated with tau pathology

(2012) Sachiko Ujiie et al.   PARKINSONISM & RELATED DISORDERS

LRRK2 G2385R and LRRK2 R1628P increase risk of Parkinson's disease in a Han Chinese population from Southern Mainland China

(2012) Xiaoli Fu et al.   PARKINSONISM & RELATED DISORDERS

LRRK2 Phosphorylates Tubulin-Associated Tau but Not the Free Molecule: LRRK2-Mediated Regulation of the Tau-Tubulin Association and Neurite Outgrowth

(2012) Fumitaka Kawakami et al.   PLoS One

Biochemical Characterization of Highly Purified Leucine-Rich Repeat Kinases 1 and 2 Demonstrates Formation of Homodimers

(2012) Laura Civiero et al.   PLoS One

Phosphorylation of 4E-BP1 in the Mammalian Brain Is Not Altered by LRRK2 Expression or Pathogenic Mutations

(2012) Alzbeta Trancikova et al.   PLoS One

Leucine-rich repeat kinase 2 (LRRK2) as a potential therapeutic target in Parkinson's disease

(2012) Byoung Dae Lee et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Brain Penetrant LRRK2 Inhibitor

(2012) Hwan Geun Choi et al.   ACS Medicinal Chemistry Letters

GTPase Activity and Neuronal Toxicity of Parkinson's Disease–Associated LRRK2 Is Regulated by ArfGAP1

(2012) Klodjan Stafa et al.   PLoS Genetics

Chemoproteomics-Based Design of Potent LRRK2-Selective Lead Compounds That Attenuate Parkinson’s Disease-Related Toxicity in Human Neurons

(2011) Nigel Ramsden et al.   ACS Chemical Biology

A Mutation in VPS35, Encoding a Subunit of the Retromer Complex, Causes Late-Onset Parkinson Disease

(2011) Alexander Zimprich et al.   AMERICAN JOURNAL OF HUMAN GENETICS

Translation Initiator EIF4G1 Mutations in Familial Parkinson Disease

(2011) Marie-Christine Chartier-Harlin et al.   AMERICAN JOURNAL OF HUMAN GENETICS

VPS35 Mutations in Parkinson Disease

(2011) Carles Vilariño-Güell et al.   AMERICAN JOURNAL OF HUMAN GENETICS

LRRK2 protein levels are determined by kinase function and are crucial for kidney and lung homeostasis in mice

(2011) Martin C. Herzig et al.   HUMAN MOLECULAR GENETICS

LRRK2 Parkinson disease mutations enhance its microtubule association

(2011) Lauren R. Kett et al.   HUMAN MOLECULAR GENETICS

Roles of the Drosophila LRRK2 homolog in Rab7-dependent lysosomal positioning

(2011) M. W. Dodson et al.   HUMAN MOLECULAR GENETICS

Inhibitors of LRRK2 kinase attenuate neurodegeneration and Parkinson-like phenotypes in Caenorhabditis elegans and Drosophila Parkinson's disease models

(2011) Zhaohui Liu et al.   HUMAN MOLECULAR GENETICS

Rac1 Protein Rescues Neurite Retraction Caused by G2019S Leucine-rich Repeat Kinase 2 (LRRK2)

(2011) Diane Chan et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Autophosphorylation in the Leucine-Rich Repeat Kinase 2 (LRRK2) GTPase Domain Modifies Kinase and GTP-Binding Activities

(2011) Philip J. Webber et al.   JOURNAL OF MOLECULAR BIOLOGY

A Rat Model of Progressive Nigral Neurodegeneration Induced by the Parkinson's Disease-Associated G2019S Mutation in LRRK2

(2011) J. Dusonchet et al.   JOURNAL OF NEUROSCIENCE

LRRK2 Controls Synaptic Vesicle Storage and Mobilization within the Recycling Pool

(2011) G. Piccoli et al.   JOURNAL OF NEUROSCIENCE

Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: a case–control study

(2011) Owen A Ross et al.   LANCET NEUROLOGY

Milestones in Parkinson's disease-Clinical and pathologic features

(2011) Glenda Halliday et al.   MOVEMENT DISORDERS

Characterization of a selective inhibitor of the Parkinson's disease kinase LRRK2

(2011) Xianming Deng et al.   Nature Chemical Biology

First neuropathological description of a patient with Parkinson’s disease and LRRK2 p.N1437H mutation

(2011) Andreas Puschmann et al.   PARKINSONISM & RELATED DISORDERS

Dopaminergic Neuronal Loss, Reduced Neurite Complexity and Autophagic Abnormalities in Transgenic Mice Expressing G2019S Mutant LRRK2

(2011) David Ramonet et al.   PLoS One

LRRK2 Kinase Activity Is Dependent on LRRK2 GTP Binding Capacity but Independent of LRRK2 GTP Binding

(2011) Jean-Marc Taymans et al.   PLoS One

Inhibition of LRRK2 kinase activity leads to dephosphorylation of Ser910/Ser935, disruption of 14-3-3 binding and altered cytoplasmic localization

(2010) Nicolas Dzamko et al.   BIOCHEMICAL JOURNAL

14-3-3 binding to LRRK2 is disrupted by multiple Parkinson's disease-associated mutations and regulates cytoplasmic localization

(2010) R. Jeremy Nichols et al.   BIOCHEMICAL JOURNAL

Kinetic Mechanistic Studies of Wild-Type Leucine-Rich Repeat Kinase2: Characterization of the Kinase and GTPase Activities

(2010) Min Liu et al.   BIOCHEMISTRY

Membrane Localization of LRRK2 Is Associated with Increased Formation of the Highly Active LRRK2 Dimer and Changes in Its Phosphorylation

(2010) Zdenek Berger et al.   BIOCHEMISTRY

Reevaluation of Phosphorylation Sites in the Parkinson Disease-associated Leucine-rich Repeat Kinase 2

(2010) Xiaojie Li et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

MKK6 binds and regulates expression of Parkinson’s disease-related protein LRRK2

(2010) Cindy H. Hsu et al.   JOURNAL OF NEUROCHEMISTRY

Insight into the mode of action of the LRRK2 Y1699C pathogenic mutant

(2010) Veronique Daniëls et al.   JOURNAL OF NEUROCHEMISTRY

LRRK2 G2019S Mutation Induces Dendrite Degeneration through Mislocalization and Phosphorylation of Tau by Recruiting Autoactivated GSK3 

(2010) C.-H. Lin et al.   JOURNAL OF NEUROSCIENCE

Enhanced Striatal Dopamine Transmission and Motor Performance with LRRK2 Overexpression in Mice Is Eliminated by Familial Parkinson's Disease Mutation G2019S

(2010) X. Li et al.   JOURNAL OF NEUROSCIENCE

Phosphopeptide Analysis Reveals Two Discrete Clusters of Phosphorylation in the N-Terminus and the Roc Domain of the Parkinson-Disease Associated Protein Kinase LRRK2

(2010) Christian Johannes Gloeckner et al.   JOURNAL OF PROTEOME RESEARCH

Novel pathogenic LRRK2 p.Asn1437His substitution in familial Parkinson's disease

(2010) Jan O. Aasly et al.   MOVEMENT DISORDERS

Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson's disease

(2010) Byoung Dae Lee et al.   NATURE MEDICINE

The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson's disease

(2010) Mark R. Cookson   NATURE REVIEWS NEUROSCIENCE

LRRK2-mediated neurodegeneration and dysfunction of dopaminergic neurons in a Caenorhabditis elegans model of Parkinson's disease

(2010) Chen Yao et al.   NEUROBIOLOGY OF DISEASE

Impaired dopaminergic neurotransmission and microtubule-associated protein tau alterations in human LRRK2 transgenic mice

(2010) H.L. Melrose et al.   NEUROBIOLOGY OF DISEASE

Mitochondrial impairment in patients with Parkinson disease with the G2019S mutation in LRRK2

(2010) H. Mortiboys et al.   NEUROLOGY

A comparative study of Lrrk2 function in primary neuronal cultures

(2010) Justus C. Dächsel et al.   PARKINSONISM & RELATED DISORDERS

LRRK2 R1398H polymorphism is associated with decreased risk of Parkinson’s disease in a Han Chinese population

(2010) Ling Chen et al.   PARKINSONISM & RELATED DISORDERS

The Parkinson's Disease Associated LRRK2 Exhibits Weaker In Vitro Phosphorylation of 4E-BP Compared to Autophosphorylation

(2010) Azad Kumar et al.   PLoS One

ARHGEF7 (BETA-PIX) Acts as Guanine Nucleotide Exchange Factor for Leucine-Rich Repeat Kinase 2

(2010) Karina Haebig et al.   PLoS One

Loss of leucine-rich repeat kinase 2 causes impairment of protein degradation pathways, accumulation of  -synuclein, and apoptotic cell death in aged mice

(2010) Y. Tong et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

GTPase Activity Plays a Key Role in the Pathobiology of LRRK2

(2010) Yulan Xiong et al.   PLoS Genetics

The progression of pathology in Parkinson's disease

(2009) Glenda Margaret Halliday et al.   Annals of the New York Academy of Sciences

The Parkinson’s disease kinase LRRK2 autophosphorylates its GTPase domain at multiple sites

(2009) Elisa Greggio et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Identification of the Autophosphorylation Sites of LRRK2

(2009) Shogo Kamikawaji et al.   BIOCHEMISTRY

The R1441C mutation alters the folding properties of the ROC domain of LRRK2

(2009) Yongchao Li et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

LRRK2 R1628P contributes to Parkinson's disease susceptibility in Chinese Han populations from mainland China

(2009) Lihua Yu et al.   BRAIN RESEARCH

Molecular pathogenesis of Parkinson disease: insights from genetic studies

(2009) Thomas Gasser   EXPERT REVIEWS IN MOLECULAR MEDICINE

Mutations in the LRRK2 Roc-COR tandem domain link Parkinson's disease to Wnt signalling pathways

(2009) Rosa M. Sancho et al.   HUMAN MOLECULAR GENETICS

Leucine-rich repeat kinase 2 interacts with Parkin, DJ-1 and PINK-1 in a Drosophila melanogaster model of Parkinson's disease

(2009) K. Venderova et al.   HUMAN MOLECULAR GENETICS

LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model

(2009) Javier Alegre-Abarrategui et al.   HUMAN MOLECULAR GENETICS

Dependence of Leucine-rich Repeat Kinase 2 (LRRK2) Kinase Activity on Dimerization

(2009) Saurabh Sen et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Leucine-rich repeat kinase 2 phosphorylates brain tubulin-beta isoforms and modulates microtubule stability - a point of convergence in Parkinsonian neurodegeneration?

(2009) Frank Gillardon   JOURNAL OF NEUROCHEMISTRY

Phosphorylation of Ezrin/Radixin/Moesin Proteins by LRRK2 Promotes the Rearrangement of Actin Cytoskeleton in Neuronal Morphogenesis

(2009) L. Parisiadou et al.   JOURNAL OF NEUROSCIENCE

Parkin Protects against LRRK2 G2019S Mutant-Induced Dopaminergic Neurodegeneration in Drosophila

(2009) C.-H. Ng et al.   JOURNAL OF NEUROSCIENCE

LRRK2 Modulates Vulnerability to Mitochondrial Dysfunction in Caenorhabditis elegans

(2009) S. Saha et al.   JOURNAL OF NEUROSCIENCE

Parkinson's disease

(2009) Andrew J Lees et al.   LANCET

LRRK2R1628P variant is a risk factor of Parkinson's disease among Han-Chinese from mainland China

(2009) Zijuan Zhang et al.   MOVEMENT DISORDERS

Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease

(2009) Wataru Satake et al.   NATURE GENETICS

Genome-wide association study reveals genetic risk underlying Parkinson's disease

(2009) Javier Simón-Sánchez et al.   NATURE GENETICS

Mutant LRRK2 R1441G BAC transgenic mice recapitulate cardinal features of Parkinson's disease

(2009) Yanping Li et al.   NATURE NEUROSCIENCE

Rapamycin activation of 4E-BP prevents parkinsonian dopaminergic neuron loss

(2009) Luke S Tain et al.   NATURE NEUROSCIENCE

It takes two to tango: regulation of G proteins by dimerization

(2009) Raphael Gasper et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Leucine-Rich Repeat Kinase 2 Regulates the Progression of Neuropathology Induced by Parkinson's-Disease-Related Mutant α-synuclein

(2009) Xian Lin et al.   NEURON

Clinical features of LRRK2 parkinsonism

(2009) Kristoffer Haugarvoll et al.   PARKINSONISM & RELATED DISORDERS

The LRRK2 G2385R variant is a risk factor for sporadic Parkinson's disease in the Korean population

(2009) Jong-Min Kim et al.   PARKINSONISM & RELATED DISORDERS

The WD40 Domain Is Required for LRRK2 Neurotoxicity

(2009) Nathan D. Jorgensen et al.   PLoS One

R1441C mutation in LRRK2 impairs dopaminergic neurotransmission in mice

(2009) Y. Tong et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Analysis of Lrrk2 R1628P as a risk factor for Parkinson's disease

(2008) Owen A. Ross et al.   ANNALS OF NEUROLOGY

Identification of compounds that inhibit the kinase activity of leucine-rich repeat kinase 2

(2008) Jason P. Covy et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

The Gly2019Ser mutation in LRRK2is not fully penetrant in familial Parkinson's disease: the GenePD study

(2008) Jeanne C Latourelle et al.   BMC Medicine

Structure of the Roc–COR domain tandem of C. tepidum, a prokaryotic homologue of the human LRRK2 Parkinson kinase

(2008) Katja Gotthardt et al.   EMBO JOURNAL

Phosphorylation of 4E-BP by LRRK2 affects the maintenance of dopaminergic neurons in Drosophila

(2008) Yuzuru Imai et al.   EMBO JOURNAL

LRRK2 regulates synaptic vesicle endocytosis

(2008) Narae Shin et al.   EXPERIMENTAL CELL RESEARCH

Investigation of leucine-rich repeat kinase 2

(2008) Vasanti S. Anand et al.   FEBS Journal

LRRK2 R1628P increases risk of Parkinson’s disease: replication evidence

(2008) E. K. Tan et al.   HUMAN GENETICS

The Parkinson Disease-associated Leucine-rich Repeat Kinase 2 (LRRK2) Is a Dimer That Undergoes Intramolecular Autophosphorylation

(2008) Elisa Greggio et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Role of autophagy in G2019S-LRRK2-associated neurite shortening in differentiated SH-SY5Y cells

(2008) Edward D. Plowey et al.   JOURNAL OF NEUROCHEMISTRY

The Roc domain of leucine-rich repeat kinase 2 is sufficient for interaction with microtubules

(2008) Payal N. Gandhi et al.   JOURNAL OF NEUROSCIENCE RESEARCH

Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study

(2008) Daniel G Healy et al.   LANCET NEUROLOGY

Lrrk2 R1441C parkinsonism is clinically similar to sporadic Parkinson disease

(2008) K. Haugarvoll et al.   NEUROLOGY

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

(2008) M. Westerlund et al.   NEUROSCIENCE

Haplotype analysis of Lrrk2 R1441H carriers with parkinsonism

(2008) Owen A. Ross et al.   PARKINSONISM & RELATED DISORDERS

A Drosophila model for LRRK2-linked parkinsonism

(2008) Z. Liu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase

(2008) J. Deng et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA