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
Products:     LRRK2

Top Publications

  1. Cookson M. The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson's disease. Nat Rev Neurosci. 2010;11:791-7 pubmed publisher
    ..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 ..
  2. Zabetian C, Yamamoto M, Lopez A, Ujike H, Mata I, Izumi Y, et al. LRRK2 mutations and risk variants in Japanese patients with Parkinson's disease. Mov Disord. 2009;24:1034-41 pubmed publisher
    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common genetic determinant of Parkinson's disease (PD) in European-derived populations, but far less is known about LRRK2 mutations and susceptibility alleles in ..
  3. Camargos S, Dornas L, Momeni P, Lees A, Hardy J, Singleton A, et al. Familial Parkinsonism and early onset Parkinson's disease in a Brazilian movement disorders clinic: phenotypic characterization and frequency of SNCA, PRKN, PINK1, and LRRK2 mutations. Mov Disord. 2009;24:662-6 pubmed publisher
    ..a standardized clinical assessment of patients followed by sequencing of PRKN, PINK1 in EOPD cases and SNCA, LRRK2 in familial Parkinsonism individuals...
  4. Greggio E, Taymans J, Zhen E, Ryder J, Vancraenenbroeck R, Beilina A, et al. The Parkinson's disease kinase LRRK2 autophosphorylates its GTPase domain at multiple sites. Biochem Biophys Res Commun. 2009;389:449-54 pubmed publisher
    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...
  5. Berwick D, Harvey K. LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6. Hum Mol Genet. 2012;21:4966-79 pubmed publisher
    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...
  6. Rubio J, Topp S, Warren L, St Jean P, Wegmann D, Kessner D, et al. Deep sequencing of the LRRK2 gene in 14,002 individuals reveals evidence of purifying selection and independent origin of the p.Arg1628Pro mutation in Europe. Hum Mutat. 2012;33:1087-98 pubmed publisher
    Genetic variation in LRRK2 predisposes to Parkinson disease (PD), which underpins its development as a therapeutic target...
  7. Greggio E. Role of LRRK2 kinase activity in the pathogenesis of Parkinson's disease. Biochem Soc Trans. 2012;40:1058-62 pubmed
    Interest in studying the biology of LRRK2 (leucine-rich repeat kinase 2) started in 2004 when missense mutations in the LRRK2 gene were linked to an inherited form of Parkinson's disease with clinical and pathological presentation ..
  8. Parisiadou L, Yu J, Sgobio C, Xie C, Liu G, Sun L, et al. LRRK2 regulates synaptogenesis and dopamine receptor activation through modulation of PKA activity. Nat Neurosci. 2014;17:367-76 pubmed publisher
    Leucine-rich repeat kinase 2 (LRRK2) is enriched in the striatal projection neurons (SPNs)...
  9. Gomez Suaga P, Luzón Toro B, Churamani D, Zhang L, Bloor Young D, Patel S, et al. Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP. Hum Mol Genet. 2012;21:511-25 pubmed publisher
    Mutations in the leucine-rich repeat kinase-2 (LRRK2) gene cause late-onset Parkinson's disease, but its physiological function has remained largely unknown...

More Information

Publications154 found, 100 shown here

  1. Wang X, Yan M, Fujioka H, Liu J, Wilson Delfosse A, Chen S, et al. LRRK2 regulates mitochondrial dynamics and function through direct interaction with DLP1. Hum Mol Genet. 2012;21:1931-44 pubmed publisher
    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...
  2. Looyenga B, Furge K, Dykema K, Koeman J, Swiatek P, Giordano T, et al. Chromosomal amplification of leucine-rich repeat kinase-2 (LRRK2) is required for oncogenic MET signaling in papillary renal and thyroid carcinomas. Proc Natl Acad Sci U S A. 2011;108:1439-44 pubmed publisher
    ..Our bioinformatic analysis identified leucine-rich repeat kinase-2 (LRRK2), which is amplified and overexpressed in papillary renal and thyroid carcinomas...
  3. Wu Y, Tan L, Fu X, Chen C, Au W, Chen L, et al. LRRK2 A419V is not associated with Parkinson's disease in different Chinese populations. PLoS ONE. 2012;7:e36123 pubmed publisher
    It has been suggested that a common LRRK2 polymorphic variant (A419V (rs34594498 C >T)) may be a risk factor among Asians (especially in Taiwan). In this study, we examined this variant in a larger and independent Taiwan cohort...
  4. Covy J, Giasson B. The G2019S pathogenic mutation disrupts sensitivity of leucine-rich repeat kinase 2 to manganese kinase inhibition. J Neurochem. 2010;115:36-46 pubmed publisher
    Mutations in leucine-rich repeat kinase-2 (LRRK2) are the most common cause of late-onset Parkinson disease...
  5. Sharma S, Bandopadhyay R, Lashley T, Renton A, Kingsbury A, Kumaran R, et al. LRRK2 expression in idiopathic and G2019S positive Parkinson's disease subjects: a morphological and quantitative study. Neuropathol Appl Neurobiol. 2011;37:777-90 pubmed publisher
    Mutations in the gene encoding leucine-rich repeat kinase-2 (LRRK2) have been established as a common genetic cause of Parkinson's disease (PD)...
  6. Gardet A, Benita Y, Li C, Sands B, Ballester I, Stevens C, et al. LRRK2 is involved in the IFN-gamma response and host response to pathogens. J Immunol. 2010;185:5577-85 pubmed publisher
    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...
  7. Bailey R, Covy J, Melrose H, Rousseau L, Watkinson R, Knight J, et al. LRRK2 phosphorylates novel tau epitopes and promotes tauopathy. Acta Neuropathol. 2013;126:809-27 pubmed publisher
    Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) are the most frequent cause of familial Parkinson's disease (PD)...
  8. Li X, Moore D, Xiong Y, Dawson T, Dawson V. Reevaluation of phosphorylation sites in the Parkinson disease-associated leucine-rich repeat kinase 2. J Biol Chem. 2010;285:29569-76 pubmed publisher
    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...
  9. Taymans J, Vancraenenbroeck R, Ollikainen P, Beilina A, Lobbestael E, De Maeyer M, et al. LRRK2 kinase activity is dependent on LRRK2 GTP binding capacity but independent of LRRK2 GTP binding. PLoS ONE. 2011;6:e23207 pubmed publisher
    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...
  10. Papkovskaia T, Chau K, Inesta Vaquera F, Papkovsky D, Healy D, Nishio K, et al. G2019S leucine-rich repeat kinase 2 causes uncoupling protein-mediated mitochondrial depolarization. Hum Mol Genet. 2012;21:4201-13 pubmed publisher
    The G2019S leucine rich repeat kinase 2 (LRRK2) mutation is the most common genetic cause of Parkinson's disease (PD), clinically and pathologically indistinguishable from idiopathic PD...
  11. Kim J, Lee J, Kim H, Kim J, Shin E, Cho J, et al. The LRRK2 G2385R variant is a risk factor for sporadic Parkinson's disease in the Korean population. Parkinsonism Relat Disord. 2010;16:85-8 pubmed publisher
    The G2385R (SNP accession no. rs34778348) and R1628P (rs33949390) variants of leucine-rich repeat kinase 2 (LRRK2, PARK8) are emerging as an important risk factor for Parkinson's disease (PD) in the ethnic Chinese and Japanese ..
  12. Sheng Z, Zhang S, Bustos D, Kleinheinz T, Le Pichon C, Dominguez S, et al. Ser1292 autophosphorylation is an indicator of LRRK2 kinase activity and contributes to the cellular effects of PD mutations. Sci Transl Med. 2012;4:164ra161 pubmed publisher
    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of familial Parkinson's disease (PD)...
  13. Hakimi M, Selvanantham T, Swinton E, Padmore R, Tong Y, Kabbach G, et al. Parkinson's disease-linked LRRK2 is expressed in circulating and tissue immune cells and upregulated following recognition of microbial structures. J Neural Transm (Vienna). 2011;118:795-808 pubmed publisher
    Sequence variants at or near the leucine-rich repeat kinase 2 (LRRK2) locus have been associated with susceptibility to three human conditions: Parkinson's disease (PD), Crohn's disease and leprosy...
  14. Hamza T, Zabetian C, Tenesa A, Laederach A, Montimurro J, Yearout D, et al. Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease. Nat Genet. 2010;42:781-5 pubmed publisher
    ..The genetic association with HLA supports the involvement of the immune system in Parkinson's disease and offers new targets for drug development. ..
  15. Tsika E, Moore D. Mechanisms of LRRK2-mediated neurodegeneration. Curr Neurol Neurosci Rep. 2012;12:251-60 pubmed publisher
    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene represent the most common cause of familial Parkinson's disease (PD), whereas common variation at the LRRK2 locus is associated with an increased risk of idiopathic PD...
  16. Lobbestael E, Zhao J, Rudenko I, Beylina A, Gao F, Wetter J, et al. Identification of protein phosphatase 1 as a regulator of the LRRK2 phosphorylation cycle. Biochem J. 2013;456:119-28 pubmed publisher
    A cluster of phosphorylation sites in LRRK2 (leucine-rich repeat kinase 2), including Ser910, Ser935, Ser955 and Ser973, is important for PD (Parkinson's disease) pathogenesis as several PD-linked LRRK2 mutants are dephosphorylated at ..
  17. Simón Sánchez J, Schulte C, Bras J, Sharma M, Gibbs J, Berg D, et al. Genome-wide association study reveals genetic risk underlying Parkinson's disease. Nat Genet. 2009;41:1308-12 pubmed publisher
    ..66, P = 7.29 x 10(-8)) and provide supporting evidence that common variation around LRRK2 modulates risk for PD (rs1491923, OR = 1.14, P = 1.55 x 10(-5))...
  18. Gan Or Z, Bar Shira A, Mirelman A, Gurevich T, Giladi N, Orr Urtreger A. The age at motor symptoms onset in LRRK2-associated Parkinson's disease is affected by a variation in the MAPT locus: a possible interaction. J Mol Neurosci. 2012;46:541-4 pubmed publisher
    ..the age of motor symptoms onset (AO) in 44 PD patients from 19 families, carriers of leucine-rich repeat kinase 2 (LRRK2) mutations, all of European and North American origin...
  19. Devine M, Kaganovich A, Ryten M, Mamais A, Trabzuni D, Manzoni C, et al. Pathogenic LRRK2 mutations do not alter gene expression in cell model systems or human brain tissue. PLoS ONE. 2011;6:e22489 pubmed publisher
    Point mutations in LRRK2 cause autosomal dominant Parkinson's disease. Despite extensive efforts to determine the mechanism of cell death in patients with LRRK2 mutations, the aetiology of LRRK2 PD is not well understood...
  20. Carballo Carbajal I, Weber Endress S, Rovelli G, Chan D, Wolozin B, Klein C, et al. Leucine-rich repeat kinase 2 induces alpha-synuclein expression via the extracellular signal-regulated kinase pathway. Cell Signal. 2010;22:821-7 pubmed publisher
    Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most frequent cause of autosomal-dominant Parkinson's disease (PD)...
  21. Li N, Tan E, Chang X, Mao X, Zhang J, Zhao D, et al. Genetic analysis of LRRK2 A419V variant in ethnic Chinese. Neurobiol Aging. 2012;33:1849.e1-3 pubmed publisher
    Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are the most common causes of autosomal dominant and sporadic forms of Parkinson's disease (PD)...
  22. Ruiz Martinez J, Gorostidi A, Goyenechea E, Alzualde A, Poza J, Rodriguez F, et al. Olfactory deficits and cardiac 123I-MIBG in Parkinson's disease related to the LRRK2 R1441G and G2019S mutations. Mov Disord. 2011;26:2026-31 pubmed publisher
    ..value these tests have in all patients with Parkinson's disease and, particularly, in those who carry mutations in LRRK2. The objective was to analyze olfactory dysfunction and the changes in cardiac I-metaiodobenzylguanidine uptake in ..
  23. Cookson M. Cellular effects of LRRK2 mutations. Biochem Soc Trans. 2012;40:1070-3 pubmed
    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...
  24. Lobbestael E, Baekelandt V, Taymans J. Phosphorylation of LRRK2: from kinase to substrate. Biochem Soc Trans. 2012;40:1102-10 pubmed
    The PD (Parkinson's disease) protein LRRK2 (leucine-rich repeat kinase 2) occurs in cells as a highly phosphorylated protein, with the majority of phosphosites clustering in the region between the ankyrin repeat and leucine-rich repeat ..
  25. Nguyen H, Byers B, Cord B, Shcheglovitov A, Byrne J, Gujar P, et al. LRRK2 mutant iPSC-derived DA neurons demonstrate increased susceptibility to oxidative stress. Cell Stem Cell. 2011;8:267-80 pubmed publisher
    ..G2019S mutation (G2019S-iPSCs) in the Leucine-Rich Repeat Kinase-2 (LRRK2) gene, the most common PD-related mutation, and their differentiation into DA neurons...
  26. Saunders Pullman R, Stanley K, Wang C, San Luciano M, Shanker V, Hunt A, et al. Olfactory dysfunction in LRRK2 G2019S mutation carriers. Neurology. 2011;77:319-24 pubmed publisher
    ..Olfaction is likely disturbed in patients with PD with leucine-rich repeat kinase (LRRK2) G2019S mutations, although the degree of impairment is debated...
  27. Moehle M, Webber P, Tse T, Sukar N, Standaert D, Desilva T, et al. LRRK2 inhibition attenuates microglial inflammatory responses. J Neurosci. 2012;32:1602-11 pubmed publisher
    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...
  28. Botta Orfila T, Ezquerra M, Pastor P, Fernández Santiago R, Pont Sunyer C, Compta Y, et al. Age at onset in LRRK2-associated PD is modified by SNCA variants. J Mol Neurosci. 2012;48:245-7 pubmed publisher
    Mutations in the leucine-rich repeat kinase 2 (LRRK2) and ?-synuclein (SNCA) genes are known genetic causes of Parkinson's disease (PD)...
  29. Kamikawaji S, Ito G, Iwatsubo T. Identification of the autophosphorylation sites of LRRK2. Biochemistry. 2009;48:10963-75 pubmed publisher
    ..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 and clinicopathological similarity to sporadic PD...
  30. Chan D, Citro A, Cordy J, Shen G, Wolozin B. Rac1 protein rescues neurite retraction caused by G2019S leucine-rich repeat kinase 2 (LRRK2). J Biol Chem. 2011;286:16140-9 pubmed publisher
    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...
  31. Niu J, Yu M, Wang C, Xu Z. Leucine-rich repeat kinase 2 disturbs mitochondrial dynamics via Dynamin-like protein. J Neurochem. 2012;122:650-8 pubmed publisher
    Mutations in Leucine-rich repeat kinase 2 (LRRK2) are the leading causes of genetically inherited Parkinson's disease (PD) identified so far...
  32. Mills R, Mulhern T, Liu F, Culvenor J, Cheng H. Prediction of the repeat domain structures and impact of parkinsonism-associated variations on structure and function of all functional domains of leucine-rich repeat kinase 2 (LRRK2). Hum Mutat. 2014;35:395-412 pubmed publisher
    Genetic variations of leucine-rich repeat kinase 2 (LRRK2) are the major cause of dominantly inherited Parkinson disease (PD)...
  33. Alegre Abarrategui J, Ansorge O, Esiri M, Wade Martins R. LRRK2 is a component of granular alpha-synuclein pathology in the brainstem of Parkinson's disease. Neuropathol Appl Neurobiol. 2008;34:272-83 pubmed
    ..Leucine-rich repeat kinase 2 (LRRK2) is the commonest mutated gene in inherited and idiopathic PD...
  34. Winner B, Melrose H, Zhao C, Hinkle K, Yue M, Kent C, et al. Adult neurogenesis and neurite outgrowth are impaired in LRRK2 G2019S mice. Neurobiol Dis. 2011;41:706-16 pubmed publisher
    ..In autosomal dominant PD, mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are frequent...
  35. Lill C, Roehr J, McQueen M, Kavvoura F, Bagade S, Schjeide B, et al. Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDGene database. PLoS Genet. 2012;8:e1002548 pubmed publisher
    ..genome-wide significant (P < 5 × 10(-8)) association with disease risk: BST1, CCDC62/HIP1R, DGKQ/GAK, GBA, LRRK2, MAPT, MCCC1/LAMP3, PARK16, SNCA, STK39, and SYT11/RAB25...
  36. Zhou H, Huang C, Tong J, Hong W, Liu Y, Xia X. Temporal expression of mutant LRRK2 in adult rats impairs dopamine reuptake. Int J Biol Sci. 2011;7:753-61 pubmed
    ..Mutation of the leucine-rich repeat kinase-2 (LRRK2) gene is associated with familial and sporadic PD, as exemplified by G2019S substitution...
  37. Yuan Y, Cao P, Smith M, Kramp K, Huang Y, Hisamoto N, et al. Dysregulated LRRK2 signaling in response to endoplasmic reticulum stress leads to dopaminergic neuron degeneration in C. elegans. PLoS ONE. 2011;6:e22354 pubmed publisher
    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...
  38. Liu Z, Lee J, Krummey S, Lu W, Cai H, Lenardo M. The kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel disease. Nat Immunol. 2011;12:1063-70 pubmed publisher
    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...
  39. Tan E, Peng R, Teo Y, Tan L, Angeles D, Ho P, et al. Multiple LRRK2 variants modulate risk of Parkinson disease: a Chinese multicenter study. Hum Mutat. 2010;31:561-8 pubmed publisher
    We and others found two polymorphic LRRK2 (leucine-rich repeat kinase 2) variants (rs34778348:G>A; p.G2385R and rs33949390:G>C; p...
  40. Yescas P, Lopez M, Monroy N, Boll M, Rodríguez Violante M, Rodríguez U, et al. Low frequency of common LRRK2 mutations in Mexican patients with Parkinson's disease. Neurosci Lett. 2010;485:79-82 pubmed publisher
    Mutations in leucine-rich repeat kinase 2 gene (LRRK2) account for as much as 5-6% of familial Parkinson's disease (PD) and 1-2% of sporadic PD...
  41. Taymans J. The GTPase function of LRRK2. Biochem Soc Trans. 2012;40:1063-9 pubmed
    b>LRRK2 (leucine-rich repeat kinase 2) is a large protein encoding multiple functional domains, including two catalytically active domains, a kinase and a GTPase domain...
  42. Gehrke S, Imai Y, SOKOL N, Lu B. Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression. Nature. 2010;466:637-41 pubmed publisher
    Gain-of-function mutations in leucine-rich repeat kinase 2 (LRRK2) cause familial as well as sporadic Parkinson's disease characterized by age-dependent degeneration of dopaminergic neurons...
  43. Bardien S, Lesage S, Brice A, Carr J. Genetic characteristics of leucine-rich repeat kinase 2 (LRRK2) associated Parkinson's disease. Parkinsonism Relat Disord. 2011;17:501-8 pubmed publisher
    ..Notably, the discovery of mutations in the LRRK2 gene in patients presenting with typical 'sporadic' PD with ages at onset in their sixties and seventies has ..
  44. Bravo San Pedro J, Niso Santano M, Gómez Sánchez R, Pizarro Estrella E, Aiastui Pujana A, Gorostidi A, et al. The LRRK2 G2019S mutant exacerbates basal autophagy through activation of the MEK/ERK pathway. Cell Mol Life Sci. 2013;70:121-36 pubmed publisher
    Mutations in leucine-rich repeat kinase 2 (LRRK2) are a major cause of familial Parkinsonism, and the G2019S mutation of LRRK2 is one of the most prevalent mutations...
  45. Hermanson S, Carlson C, Riddle S, Zhao J, Vogel K, Nichols R, et al. Screening for novel LRRK2 inhibitors using a high-throughput TR-FRET cellular assay for LRRK2 Ser935 phosphorylation. PLoS ONE. 2012;7:e43580 pubmed publisher
    Mutations in the leucine-rich repeat kinase-2 (LRRK2) have been linked to Parkinson's disease...
  46. Jasinska Myga B, Kachergus J, Vilariño Güell C, Wider C, Soto Ortolaza A, Kefi M, et al. Comprehensive sequencing of the LRRK2 gene in patients with familial Parkinson's disease from North Africa. Mov Disord. 2010;25:2052-8 pubmed publisher
    The LRRK2 gene is a key player in Parkinson's disease (PD), however prevalence and pathogenicity of LRRK2 variants remain to be investigated in ethnically diverse populations...
  47. Zach S, Felk S, Gillardon F. Signal transduction protein array analysis links LRRK2 to Ste20 kinases and PKC zeta that modulate neuronal plasticity. PLoS ONE. 2010;5:e13191 pubmed publisher
    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...
  48. Fraser K, Moehle M, Daher J, Webber P, Williams J, Stewart C, et al. LRRK2 secretion in exosomes is regulated by 14-3-3. Hum Mol Genet. 2013;22:4988-5000 pubmed publisher
    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause late-onset Parkinson's disease (PD). Emerging evidence suggests a role for LRRK2 in the endocytic pathway...
  49. Kumari U, Tan E. LRRK2 in Parkinson's disease: genetic and clinical studies from patients. FEBS J. 2009;276:6455-63 pubmed publisher
    Mutations in leucine-rich repeat kinase 2 (LRRK2) (PARK8) are associated with both familial and sporadic forms of Parkinson's disease...
  50. Xiong Y, Dawson V, Dawson T. LRRK2 GTPase dysfunction in the pathogenesis of Parkinson's disease. Biochem Soc Trans. 2012;40:1074-9 pubmed
    Mutations in the LRRK2 (leucine-rich repeat kinase 2) gene are the most frequent genetic cause of PD (Parkinson's disease), and these mutations play important roles in sporadic PD...
  51. Wu Chou Y, Chen Y, Yeh T, Chang H, Weng Y, Lai S, et al. Genetic variants of SNCA and LRRK2 genes are associated with sporadic PD susceptibility: a replication study in a Taiwanese cohort. Parkinsonism Relat Disord. 2013;19:251-5 pubmed publisher
    ..We here performed a gene-based case-control association study to scrutinize whether genetic variants in SNCA and LRRK2 genes could predispose to sporadic, late-onset form of PD in Taiwanese population...
  52. Marker D, Puccini J, Mockus T, Barbieri J, Lu S, Gelbard H. LRRK2 kinase inhibition prevents pathological microglial phagocytosis in response to HIV-1 Tat protein. J Neuroinflammation. 2012;9:261 pubmed publisher
    ..We have identified leucine-rich repeat kinase 2 (LRRK2) as a novel regulator of microglial phagocytosis and activation in an in vitro model of HANDs, and hypothesize ..
  53. Lin C, Tsai P, Wu R, Chien C. LRRK2 G2019S mutation induces dendrite degeneration through mislocalization and phosphorylation of tau by recruiting autoactivated GSK3ß. J Neurosci. 2010;30:13138-49 pubmed publisher
    ..features of Parkinson's disease (PD) with autosomal-dominant mutations in leucine-rich repeat kinase 2 (LRRK2)...
  54. Haebig K, Gloeckner C, Miralles M, Gillardon F, Schulte C, Riess O, et al. ARHGEF7 (Beta-PIX) acts as guanine nucleotide exchange factor for leucine-rich repeat kinase 2. PLoS ONE. 2010;5:e13762 pubmed publisher
    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...
  55. Drolet R, Sanders J, Kern J. Leucine-rich repeat kinase 2 (LRRK2) cellular biology: a review of recent advances in identifying physiological substrates and cellular functions. J Neurogenet. 2011;25:140-51 pubmed publisher
    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...
  56. Vancraenenbroeck R, Lobbestael E, Weeks S, Strelkov S, Baekelandt V, Taymans J, et al. Expression, purification and preliminary biochemical and structural characterization of the leucine rich repeat namesake domain of leucine rich repeat kinase 2. Biochim Biophys Acta. 2012;1824:450-60 pubmed publisher
    Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson's disease...
  57. Sen S, Webber P, West A. Dependence of leucine-rich repeat kinase 2 (LRRK2) kinase activity on dimerization. J Biol Chem. 2009;284:36346-56 pubmed publisher
    Dominant missense mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common known genetic cause of Parkinson disease...
  58. Sossi V, de la Fuente Fernandez R, Nandhagopal R, Schulzer M, Mckenzie J, Ruth T, et al. Dopamine turnover increases in asymptomatic LRRK2 mutations carriers. Mov Disord. 2010;25:2717-23 pubmed publisher
    ..Eight subjects from families at increased risk of PD due to LRRK2 mutation were investigated...
  59. Mirelman A, Gurevich T, Giladi N, Bar Shira A, Orr Urtreger A, Hausdorff J. Gait alterations in healthy carriers of the LRRK2 G2019S mutation. Ann Neurol. 2011;69:193-7 pubmed publisher
    To test for an association between the LRRK2-G2019S mutation and gait, we studied 52 first-degree relatives of patients with Parkinson's disease (PD) who carry this mutation...
  60. Nalls M, Plagnol V, Hernandez D, Sharma M, Sheerin U, Saad M, et al. Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies. Lancet. 2011;377:641-9 pubmed publisher
    ..Six were previously identified loci (MAPT, SNCA, HLA-DRB5, BST1, GAK and LRRK2) and five were newly identified loci (ACMSD, STK39, MCCC1/LAMP3, SYT11, and CCDC62/HIP1R)...
  61. Kumar A, Greggio E, Beilina A, Kaganovich A, Chan D, Taymans J, et al. The Parkinson's disease associated LRRK2 exhibits weaker in vitro phosphorylation of 4E-BP compared to autophosphorylation. PLoS ONE. 2010;5:e8730 pubmed publisher
    Mutations in the gene encoding Leucine-rich repeat kinase 2 (LRRK2) are the most common cause of inherited Parkinson's disease (PD)...
  62. Mutez E, Larvor L, Lepretre F, Mouroux V, Hamalek D, Kerckaert J, et al. Transcriptional profile of Parkinson blood mononuclear cells with LRRK2 mutation. Neurobiol Aging. 2011;32:1839-48 pubmed publisher
    ..healthy controls and from Parkinson's disease (PD) patients carrying the most frequently found mutation of the LRRK2 gene (G2019S)...
  63. Mills R, Mulhern T, Cheng H, Culvenor J. Analysis of LRRK2 accessory repeat domains: prediction of repeat length, number and sites of Parkinson's disease mutations. Biochem Soc Trans. 2012;40:1086-9 pubmed
    Various investigators have identified the major domain organization of LRRK2 (leucine-rich repeat kinase 2), which includes a GTPase ROC (Ras of complex proteins) domain followed by a COR (C-terminal of ROC) domain and a protein kinase ..
  64. Caesar M, Zach S, Carlson C, Brockmann K, Gasser T, Gillardon F. Leucine-rich repeat kinase 2 functionally interacts with microtubules and kinase-dependently modulates cell migration. Neurobiol Dis. 2013;54:280-8 pubmed publisher
    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...
  65. Kett L, Boassa D, Ho C, Rideout H, Hu J, Terada M, et al. LRRK2 Parkinson disease mutations enhance its microtubule association. Hum Mol Genet. 2012;21:890-9 pubmed publisher
    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...
  66. Cho H, Liu G, Jin S, Parisiadou L, Xie C, Yu J, et al. MicroRNA-205 regulates the expression of Parkinson's disease-related leucine-rich repeat kinase 2 protein. Hum Mol Genet. 2013;22:608-20 pubmed publisher
    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)...
  67. MacLeod D, Rhinn H, Kuwahara T, Zolin A, Di Paolo G, McCabe B, et al. RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson's disease risk. Neuron. 2013;77:425-39 pubmed publisher
    ..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 ..
  68. Silveira Moriyama L, Munhoz R, de J Carvalho M, Raskin S, Rogaeva E, de C Aguiar P, et al. Olfactory heterogeneity in LRRK2 related Parkinsonism. Mov Disord. 2010;25:2879-83 pubmed publisher
    b>LRRK2 mutations can cause familial and sporadic Parkinson's disease (PD) with Lewy-body pathology at post-mortem. Studies of olfaction in LRRK2 are sparse and incongruent...
  69. Ross O, Soto Ortolaza A, Heckman M, Aasly J, Abahuni N, Annesi G, et al. Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: a case-control study. Lancet Neurol. 2011;10:898-908 pubmed publisher
    Background The leucine-rich repeat kinase 2 gene (LRRK2) harbours highly penetrant mutations that are linked to familial parkinsonism...
  70. Ferree A, Guillily M, Li H, Smith K, Takashima A, Squillace R, et al. Regulation of physiologic actions of LRRK2: focus on autophagy. Neurodegener Dis. 2012;10:238-41 pubmed publisher
    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 ?-synuclein, tau or neither protein...
  71. Ohta E, Kawakami F, Kubo M, Obata F. LRRK2 directly phosphorylates Akt1 as a possible physiological substrate: impairment of the kinase activity by Parkinson's disease-associated mutations. FEBS Lett. 2011;585:2165-70 pubmed publisher
    b>LRRK2 is the causal molecule for autosomal-dominant familial Parkinson's disease, although its true function, including its physiological substrates, remains unknown...
  72. Beilina A, Rudenko I, Kaganovich A, Civiero L, Chau H, Kalia S, et al. Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease. Proc Natl Acad Sci U S A. 2014;111:2626-31 pubmed publisher
    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...
  73. Liao J, Wu C, Burlak C, Zhang S, Sahm H, Wang M, et al. Parkinson disease-associated mutation R1441H in LRRK2 prolongs the "active state" of its GTPase domain. Proc Natl Acad Sci U S A. 2014;111:4055-60 pubmed publisher
    Mutation in leucine-rich-repeat kinase 2 (LRRK2) is a common cause of Parkinson disease (PD). A disease-causing point mutation R1441H/G/C in the GTPase domain of LRRK2 leads to overactivation of its kinase domain...
  74. Alcalay R, Mejia Santana H, Tang M, Rakitin B, Rosado L, Ross B, et al. Self-report of cognitive impairment and mini-mental state examination performance in PRKN, LRRK2, and GBA carriers with early onset Parkinson's disease. J Clin Exp Neuropsychol. 2010;32:775-9 pubmed publisher
    ..impairment in 699 EOPD participants genotyped for mutations in parkin (PRKN), leucine-rich repeat kinase-2 (LRRK2), and GBA...
  75. San Luciano M, Lipton R, Wang C, Katz M, Zimmerman M, Sanders A, et al. Clinical expression of LRRK2 G2019S mutations in the elderly. Mov Disord. 2010;25:2571-6 pubmed publisher
    Mutations in the leucine-rich repeat kinase 2 gene (LRRK2, PARK8) are the most commonly identified monogenic etiology of Parkinson disease (PD)...
  76. Migheli R, Del Giudice M, Spissu Y, Sanna G, Xiong Y, Dawson T, et al. LRRK2 affects vesicle trafficking, neurotransmitter extracellular level and membrane receptor localization. PLoS ONE. 2013;8:e77198 pubmed publisher
    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...
  77. Hsu C, Chan D, Wolozin B. LRRK2 and the stress response: interaction with MKKs and JNK-interacting proteins. Neurodegener Dis. 2010;7:68-75 pubmed publisher
    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...
  78. Aasly J, Vilariño Güell C, Dachsel J, Webber P, West A, Haugarvoll K, et al. Novel pathogenic LRRK2 p.Asn1437His substitution in familial Parkinson's disease. Mov Disord. 2010;25:2156-63 pubmed publisher
    ..Genetic studies have revealed a novel pathogenic LRRK2 mutation c.4309 A>C (p.Asn1437His) that co-segregates with disease manifestation (LOD = 3.15, ? = 0)...
  79. Angeles D, Gan B, Onstead L, Zhao Y, Lim K, Dachsel J, et al. Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3 exacerbating oxidative stress-induced neuronal death. Hum Mutat. 2011;32:1390-7 pubmed publisher
    Mutations in the leucine rich repeat kinase 2 (LRRK2) gene are responsible for autosomal dominant and sporadic Parkinson disease (PD), possibly exerting their effects via a toxic gain of function. A common p...
  80. Kawakami F, Yabata T, Ohta E, Maekawa T, Shimada N, Suzuki M, et al. LRRK2 phosphorylates tubulin-associated tau but not the free molecule: LRRK2-mediated regulation of the tau-tubulin association and neurite outgrowth. PLoS ONE. 2012;7:e30834 pubmed publisher
    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)...
  81. Zhang F, Huang W, Chen S, Sun L, Liu H, Li Y, et al. Genomewide association study of leprosy. N Engl J Med. 2009;361:2609-18 pubmed publisher
    ..10x10(-5)) with a SNP in LRRK2. The associations between the SNPs in C13orf31, LRRK2, NOD2, and RIPK2 and multibacillary leprosy were stronger ..
  82. Lee B, Shin J, VanKampen J, Petrucelli L, West A, Ko H, et al. Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson's disease. Nat Med. 2010;16:998-1000 pubmed publisher
    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...
  83. Lee S, Liu H, Lin W, Guo H, Lu B. LRRK2 kinase regulates synaptic morphology through distinct substrates at the presynaptic and postsynaptic compartments of the Drosophila neuromuscular junction. J Neurosci. 2010;30:16959-69 pubmed publisher
    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 ..
  84. Esposito G, Ana Clara F, Verstreken P. Synaptic vesicle trafficking and Parkinson's disease. Dev Neurobiol. 2012;72:134-44 pubmed publisher
    ..This article reviews our current understanding for a role of causative PD genes in the SV cycle and speculates on the potential role of aberrant SV trafficking in the neurodegenerative cascade of PD. ..
  85. Ohta E, Katayama Y, Kawakami F, Yamamoto M, Tajima K, Maekawa T, et al. 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. Biochem Biophys Res Commun. 2009;390:710-5 pubmed publisher
    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...
  86. Liu M, Kang S, Ray S, Jackson J, Zaitsev A, Gerber S, et al. Kinetic, mechanistic, and structural modeling studies of truncated wild-type leucine-rich repeat kinase 2 and the G2019S mutant. Biochemistry. 2011;50:9399-408 pubmed publisher
    Leucine-rich repeat kinase 2 (LRRK2), a large and complex protein that possesses two enzymatic properties, kinase and GTPase, is one of the major genetic factors in Parkinson's disease (PD)...
  87. Webber P, Smith A, Sen S, Renfrow M, Mobley J, West A. Autophosphorylation in the leucine-rich repeat kinase 2 (LRRK2) GTPase domain modifies kinase and GTP-binding activities. J Mol Biol. 2011;412:94-110 pubmed publisher
    The leucine-rich repeat kinase 2 (LRRK2) protein has both guanosine triphosphatase (GTPase) and kinase activities, and mutation in either enzymatic domain can cause late-onset Parkinson disease...
  88. Ujiie S, Hatano T, Kubo S, Imai S, Sato S, Uchihara T, et al. LRRK2 I2020T mutation is associated with tau pathology. Parkinsonism Relat Disord. 2012;18:819-23 pubmed publisher
    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of autosomal-dominant familial Parkinson's disease (FPD)...
  89. Matta S, Van Kolen K, da Cunha R, van den Bogaart G, Mandemakers W, Miskiewicz K, et al. LRRK2 controls an EndoA phosphorylation cycle in synaptic endocytosis. Neuron. 2012;75:1008-21 pubmed publisher
    b>LRRK2 is a kinase mutated in Parkinson's disease, but how the protein affects synaptic function remains enigmatic. We identified LRRK2 as a critical regulator of EndophilinA...
  90. Alcalay R, Mirelman A, Saunders Pullman R, Tang M, Mejia Santana H, Raymond D, et al. Parkinson disease phenotype in Ashkenazi Jews with and without LRRK2 G2019S mutations. Mov Disord. 2013;28:1966-71 pubmed publisher
    The phenotype of Parkinson's disease (PD) in patients with and without leucine-rich repeat kinase 2 (LRRK2) G2019S mutations reportedly is similar; however, large, uniformly evaluated series are lacking...
  91. Gilsbach B, Ho F, Vetter I, Van Haastert P, Wittinghofer A, Kortholt A. Roco kinase structures give insights into the mechanism of Parkinson disease-related leucine-rich-repeat kinase 2 mutations. Proc Natl Acad Sci U S A. 2012;109:10322-7 pubmed publisher
    Mutations in human leucine-rich-repeat kinase 2 (LRRK2) have been found to be the most frequent cause of late-onset Parkinson disease...
  92. Orenstein S, Kuo S, Tasset I, Arias E, Koga H, Fernandez Carasa I, et al. Interplay of LRRK2 with chaperone-mediated autophagy. Nat Neurosci. 2013;16:394-406 pubmed publisher
    Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson's disease...