Lrrk2

Summary

Gene Symbol: Lrrk2
Description: leucine-rich repeat kinase 2
Alias: leucine-rich repeat serine/threonine-protein kinase 2
Species: rat
Products:     Lrrk2

Top Publications

  1. Kachergus J, Mata I, Hulihan M, Taylor J, Lincoln S, Aasly J, et al. Identification of a novel LRRK2 mutation linked to autosomal dominant parkinsonism: evidence of a common founder across European populations. Am J Hum Genet. 2005;76:672-80 pubmed
    ..dominant parkinsonism has been attributed to pathogenic amino acid substitutions in leucine-rich repeat kinase 2 (LRRK2)...
  2. Biskup S, Moore D, Celsi F, Higashi S, West A, Andrabi S, et al. Localization of LRRK2 to membranous and vesicular structures in mammalian brain. Ann Neurol. 2006;60:557-69 pubmed
    ..disease encodes a large novel protein of unknown biological function termed leucine-rich repeat kinase 2 (LRRK2). The studies herein explore the localization of LRRK2 in the mammalian brain...
  3. Westerlund M, Ran C, Borgkvist A, Sterky F, Lindqvist E, Lundströmer K, et al. Lrrk2 and alpha-synuclein are co-regulated in rodent striatum. Mol Cell Neurosci. 2008;39:586-91 pubmed publisher
    b>LRRK2, alpha-synuclein, UCH-L1 and DJ-1 are implicated in the etiology of Parkinson's disease...
  4. Deng J, Lewis P, Greggio E, Sluch E, Beilina A, Cookson M. Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase. Proc Natl Acad Sci U S A. 2008;105:1499-504 pubmed publisher
    Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of Parkinson's disease (PD). LRRK2 contains a Ras of complex proteins (ROC) domain that may act as a GTPase to regulate its protein kinase activity...
  5. Gloeckner C, Schumacher A, Boldt K, Ueffing M. The Parkinson disease-associated protein kinase LRRK2 exhibits MAPKKK activity and phosphorylates MKK3/6 and MKK4/7, in vitro. J Neurochem. 2009;109:959-68 pubmed publisher
    Autosomal dominant mutations in the human Leucine-Rich Repeat Kinase 2 (LRRK2) gene represent the most common monogenetic cause of Parkinson disease (PD) and increased kinase activity observed in pathogenic mutants of LRRK2 is most ..
  6. 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 ..
  7. Smith W, Pei Z, Jiang H, Moore D, Liang Y, West A, et al. Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degeneration. Proc Natl Acad Sci U S A. 2005;102:18676-81 pubmed
    ..Mutations in leucine-rich repeat kinase 2 (LRRK2) cause autosomal-dominant Parkinsonism with clinical features of PD and with pleomorphic pathology including ..
  8. 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...
  9. West A, Moore D, Choi C, Andrabi S, Li X, Dikeman D, et al. Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity. Hum Mol Genet. 2007;16:223-32 pubmed
    Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) cause late-onset Parkinson's disease indistinguishable from idiopathic disease...

More Information

Publications76

  1. Tong Y, Yamaguchi H, Giaime E, Boyle S, Kopan R, Kelleher R, et al. Loss of leucine-rich repeat kinase 2 causes impairment of protein degradation pathways, accumulation of alpha-synuclein, and apoptotic cell death in aged mice. Proc Natl Acad Sci U S A. 2010;107:9879-84 pubmed publisher
    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...
  2. Greggio E, Zambrano I, Kaganovich A, Beilina A, Taymans J, Daniëls V, et al. The Parkinson disease-associated leucine-rich repeat kinase 2 (LRRK2) is a dimer that undergoes intramolecular autophosphorylation. J Biol Chem. 2008;283:16906-14 pubmed publisher
    Mutations in leucine-rich repeat kinase 2 (LRRK2) are a common cause of familial and apparently sporadic Parkinson disease. LRRK2 is a multidomain protein kinase with autophosphorylation activity...
  3. Miklossy J, Qing H, Guo J, Yu S, Wszolek Z, Calne D, et al. Lrrk2 and chronic inflammation are linked to pallido-ponto-nigral degeneration caused by the N279K tau mutation. Acta Neuropathol. 2007;114:243-54 pubmed
    Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have been identified in families with autosomal dominant late-onset Parkinson disease (PD)...
  4. 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...
  5. Berger Z, Smith K, LaVoie M. Membrane localization of LRRK2 is associated with increased formation of the highly active LRRK2 dimer and changes in its phosphorylation. Biochemistry. 2010;49:5511-23 pubmed publisher
    Autosomal dominant mutations in leucine rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease (PD)...
  6. 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...
  7. 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...
  8. 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...
  9. Daniëls V, Vancraenenbroeck R, Law B, Greggio E, Lobbestael E, Gao F, et al. Insight into the mode of action of the LRRK2 Y1699C pathogenic mutant. J Neurochem. 2011;116:304-15 pubmed publisher
    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most prevalent known cause of autosomal dominant Parkinson's disease...
  10. Gloeckner C, Kinkl N, Schumacher A, Braun R, O Neill E, Meitinger T, et al. The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity. Hum Mol Genet. 2006;15:223-32 pubmed
    Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have been recently identified in families with autosomal dominant late-onset Parkinson disease (PD)...
  11. 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...
  12. Vitte J, Traver S, Maués De Paula A, Lesage S, Rovelli G, Corti O, et al. Leucine-rich repeat kinase 2 is associated with the endoplasmic reticulum in dopaminergic neurons and accumulates in the core of Lewy bodies in Parkinson disease. J Neuropathol Exp Neurol. 2010;69:959-72 pubmed publisher
    Mutation of the leucine-rich repeat kinase 2 (LRRK2) gene is the most frequent genetic cause of Parkinson disease (PD)...
  13. Ness D, Ren Z, Gardai S, Sharpnack D, Johnson V, Brennan R, et al. Leucine-rich repeat kinase 2 (LRRK2)-deficient rats exhibit renal tubule injury and perturbations in metabolic and immunological homeostasis. PLoS ONE. 2013;8:e66164 pubmed publisher
    Genetic evidence links mutations in the LRRK2 gene with an increased risk of Parkinson's disease, for which no neuroprotective or neurorestorative therapies currently exist...
  14. 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...
  15. Shin N, Jeong H, Kwon J, Heo H, Kwon J, Yun H, et al. LRRK2 regulates synaptic vesicle endocytosis. Exp Cell Res. 2008;314:2055-65 pubmed publisher
    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)...
  16. Hatano T, Kubo S, Imai S, Maeda M, Ishikawa K, Mizuno Y, et al. Leucine-rich repeat kinase 2 associates with lipid rafts. Hum Mol Genet. 2007;16:678-90 pubmed
    Leucine-Rich Repeat Kinase 2 (LRRK2) is a causative gene for the autosomal dominant form of Parkinson's disease (PD)...
  17. Lewis P, Greggio E, Beilina A, Jain S, Baker A, Cookson M. The R1441C mutation of LRRK2 disrupts GTP hydrolysis. Biochem Biophys Res Commun. 2007;357:668-71 pubmed
    Mutations in Leucine Rich Repeat Kinase 2 (LRRK2) are the leading genetic cause of Parkinson's disease (PD)...
  18. Klein C, Rovelli G, Springer W, Schall C, Gasser T, Kahle P. Homo- and heterodimerization of ROCO kinases: LRRK2 kinase inhibition by the LRRK2 ROCO fragment. J Neurochem. 2009;111:703-15 pubmed publisher
    Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) are the most common cause of autosomal-dominant familial and late-onset sporadic Parkinson's disease (PD)...
  19. Li X, Wang Q, Pan N, Lee S, Zhao Y, Chait B, et al. Phosphorylation-dependent 14-3-3 binding to LRRK2 is impaired by common mutations of familial Parkinson's disease. PLoS ONE. 2011;6:e17153 pubmed publisher
    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)...
  20. Alegre Abarrategui J, Christian H, Lufino M, Mutihac R, Venda L, Ansorge O, et al. LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model. Hum Mol Genet. 2009;18:4022-34 pubmed publisher
    Leucine rich repeat kinase 2 (LRRK2) mutations are the most common genetic cause of Parkinson's disease (PD) although LRRK2 function remains unclear...
  21. Westerlund M, Belin A, Anvret A, Bickford P, Olson L, Galter D. 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. Neuroscience. 2008;152:429-36 pubmed publisher
    Mutations in leucine-rich repeat kinase 2 (LRRK2) constitute the most common known cause of Parkinson's disease (PD), accounting for both familial and sporadic forms of the disease...
  22. Melrose H, Dachsel J, Behrouz B, Lincoln S, Yue M, Hinkle K, et al. Impaired dopaminergic neurotransmission and microtubule-associated protein tau alterations in human LRRK2 transgenic mice. Neurobiol Dis. 2010;40:503-17 pubmed publisher
    Mutations in the Leucine Rich Repeat Kinase 2 (LRRK2) gene, first described in 2004 have now emerged as the most important genetic finding in both autosomal dominant and sporadic Parkinson's disease (PD)...
  23. Xiong Y, Yuan C, Chen R, Dawson T, Dawson V. ArfGAP1 is a GTPase activating protein for LRRK2: reciprocal regulation of ArfGAP1 by LRRK2. J Neurosci. 2012;32:3877-86 pubmed publisher
    ..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...
  24. Civiero L, Vancraenenbroeck R, Belluzzi E, Beilina A, Lobbestael E, Reyniers L, et al. Biochemical characterization of highly purified leucine-rich repeat kinases 1 and 2 demonstrates formation of homodimers. PLoS ONE. 2012;7:e43472 pubmed publisher
    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)...
  25. 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)...
  26. Macleod D, Dowman J, Hammond R, Leete T, Inoue K, Abeliovich A. The familial Parkinsonism gene LRRK2 regulates neurite process morphology. Neuron. 2006;52:587-93 pubmed
    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...
  27. Saunders Pullman R, Barrett M, Stanley K, Luciano M, Shanker V, Severt L, et al. LRRK2 G2019S mutations are associated with an increased cancer risk in Parkinson disease. Mov Disord. 2010;25:2536-41 pubmed publisher
    Leucine rich repeat kinase (LRRK2) G2019S mutations are presumed to cause PD through a toxic gain of function of the protein kinase...
  28. West A, Moore D, Biskup S, Bugayenko A, Smith W, Ross C, et al. Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc Natl Acad Sci U S A. 2005;102:16842-7 pubmed
    Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) cause late-onset Parkinson's disease (PD) with a clinical appearance indistinguishable from idiopathic PD...
  29. Taymans J, Van den Haute C, Baekelandt V. Distribution of PINK1 and LRRK2 in rat and mouse brain. J Neurochem. 2006;98:951-61 pubmed
    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...
  30. Smith W, Pei Z, Jiang H, Dawson V, Dawson T, Ross C. Kinase activity of mutant LRRK2 mediates neuronal toxicity. Nat Neurosci. 2006;9:1231-3 pubmed
    Mutations in the the leucine-rich repeat kinase-2 (LRRK2) gene cause autosomal-dominant Parkinson disease and some cases of sporadic Parkinson disease...
  31. Ito G, Okai T, Fujino G, Takeda K, Ichijo H, Katada T, et al. GTP binding is essential to the protein kinase activity of LRRK2, a causative gene product for familial Parkinson's disease. Biochemistry. 2007;46:1380-8 pubmed
    Leucine-rich repeat kinase 2 (LRRK2), a product of a causative gene for the autosomal-dominant form of familial Parkinson's disease (PARK8), harbors a Ras-like small GTP binding protein-like (ROC) domain besides the kinase domain, ..
  32. Sancho R, Law B, Harvey K. Mutations in the LRRK2 Roc-COR tandem domain link Parkinson's disease to Wnt signalling pathways. Hum Mol Genet. 2009;18:3955-68 pubmed publisher
    Mutations in PARK8, encoding LRRK2, are the most common known cause of Parkinson's disease. The LRRK2 Roc-COR tandem domain exhibits GTPase activity controlling LRRK2 kinase activity via an intramolecular process...
  33. 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 ..
  34. 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...
  35. 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...
  36. 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...
  37. 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...
  38. Daher J, Abdelmotilib H, Hu X, Volpicelli Daley L, Moehle M, Fraser K, et al. Leucine-rich Repeat Kinase 2 (LRRK2) Pharmacological Inhibition Abates α-Synuclein Gene-induced Neurodegeneration. J Biol Chem. 2015;290:19433-44 pubmed publisher
    ..Genetic and biochemical studies implicate α-synuclein and leucine-rich repeat kinase 2 (LRRK2) in late-onset PD. LRRK2 kinase activity has been linked to neurodegenerative pathways...
  39. 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...
  40. 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...
  41. Manzoni C, Mamais A, Dihanich S, Abeti R, Soutar M, Plun Favreau H, et al. Inhibition of LRRK2 kinase activity stimulates macroautophagy. Biochim Biophys Acta. 2013;1833:2900-2910 pubmed publisher
    Leucine Rich Repeat Kinase 2 (LRRK2) is one of the most important genetic contributors to Parkinson's disease. LRRK2 has been implicated in a number of cellular processes, including macroautophagy...
  42. 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...
  43. Brockmann K, Gröger A, Di Santo A, Liepelt I, Schulte C, Klose U, et al. Clinical and brain imaging characteristics in leucine-rich repeat kinase 2-associated PD and asymptomatic mutation carriers. Mov Disord. 2011;26:2335-42 pubmed publisher
    The objective of this research was to evaluate a possible endophenotype in leucine-rich repeat kinase 2 (LRRK2)-associated Parkinson's disease (PD)...
  44. Seki N, Takahashi Y, Tomiyama H, Rogaeva E, Murayama S, Mizuno Y, et al. Comprehensive mutational analysis of LRRK2 reveals variants supporting association with autosomal dominant Parkinson's disease. J Hum Genet. 2011;56:671-5 pubmed publisher
    ..To date, six causative genes have been identified including LRRK2, whose mutations are the most frequent in autosomal dominant PD (Ad-PD)...
  45. Cui J, Yu M, Niu J, Yue Z, Xu Z. Expression of leucine-rich repeat kinase 2 (LRRK2) inhibits the processing of uMtCK to induce cell death in a cell culture model system. Biosci Rep. 2011;31:429-37 pubmed publisher
    PD (Parkinson's disease) is the most common neurodegenerative movement disorder. Mutations in LRRK2 (leucine-rich repeat kinase 2) gene are linked to the most common inherited and sporadic PD...
  46. Chen L, Zhang S, Liu Y, Hong H, Wang H, Zheng Y, et al. LRRK2 R1398H polymorphism is associated with decreased risk of Parkinson's disease in a Han Chinese population. Parkinsonism Relat Disord. 2011;17:291-2 pubmed publisher
  47. Cirnaru M, Marte A, Belluzzi E, Russo I, Gabrielli M, Longo F, et al. LRRK2 kinase activity regulates synaptic vesicle trafficking and neurotransmitter release through modulation of LRRK2 macro-molecular complex. Front Mol Neurosci. 2014;7:49 pubmed publisher
    Mutations in Leucine-rich repeat kinase 2 gene (LRRK2) are associated with familial and sporadic Parkinson's disease (PD)...
  48. Venderova K, Kabbach G, Abdel Messih E, Zhang Y, Parks R, Imai Y, et al. Leucine-Rich Repeat Kinase 2 interacts with Parkin, DJ-1 and PINK-1 in a Drosophila melanogaster model of Parkinson's disease. Hum Mol Genet. 2009;18:4390-404 pubmed publisher
    Mutations in the LRRK2 gene are the most common genetic cause of familial Parkinson's disease (PD). However, its physiological and pathological functions are unknown...
  49. Roth J, Eichhorn M. Down-regulation of LRRK2 in control and DAT transfected HEK cells increases manganese-induced oxidative stress and cell toxicity. Neurotoxicology. 2013;37:100-7 pubmed publisher
    ..Of the other Parkinson-linked genes, mutations in LRRK2, an autosomal dominant gene, represent another likely candidate involved in the development of manganism...
  50. Ohta E, Kawakami F, Kubo M, Obata F. Dominant-negative effects of LRRK2 heterodimers: a possible mechanism of neurodegeneration in Parkinson's disease caused by LRRK2 I2020T mutation. Biochem Biophys Res Commun. 2013;430:560-6 pubmed publisher
    Leucine-rich repeat kinase 2 (LRRK2) is the molecule responsible for autosomal-dominant Parkinson's disease (PD), PARK8, but the etiologic effects of its mutation remain unknown...
  51. Zechel S, Meinhardt A, Unsicker K, Von Bohlen Und Halbach O. Expression of leucine-rich-repeat-kinase 2 (LRRK2) during embryonic development. Int J Dev Neurosci. 2010;28:391-9 pubmed publisher
    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...
  52. Guaitoli G, Raimondi F, Gilsbach B, Gómez Llorente Y, Deyaert E, Renzi F, et al. Structural model of the dimeric Parkinson's protein LRRK2 reveals a compact architecture involving distant interdomain contacts. Proc Natl Acad Sci U S A. 2016;113:E4357-66 pubmed publisher
    Leucine-rich repeat kinase 2 (LRRK2) is a large, multidomain protein containing two catalytic domains: a Ras of complex proteins (Roc) G-domain and a kinase domain...
  53. Nakamura N, Shimaoka Y, Tougan T, Onda H, Okuzaki D, Zhao H, et al. Isolation and expression profiling of genes upregulated in bone marrow-derived mononuclear cells of rheumatoid arthritis patients. DNA Res. 2006;13:169-83 pubmed
    ..We propose that the expression profiling of these AURA genes may improve our understanding of the pathogenesis of RA. ..
  54. Cooper O, Seo H, Andrabi S, Guardia Laguarta C, Graziotto J, Sundberg M, et al. Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson's disease. Sci Transl Med. 2012;4:141ra90 pubmed publisher
    ..PD patients and presymptomatic individuals carrying mutations in the PINK1 (PTEN-induced putative kinase 1) and LRRK2 (leucine-rich repeat kinase 2) genes, and compared them to those of healthy control subjects...
  55. Pereira C, Miguel Martins L, Saraiva L. LRRK2, but not pathogenic mutants, protects against H2O2 stress depending on mitochondrial function and endocytosis in a yeast model. Biochim Biophys Acta. 2014;1840:2025-31 pubmed publisher
    Mutations in LRRK2 are the most common genetic cause of Parkinson's disease (PD)...
  56. Sloan M, Alegre Abarrategui J, Potgieter D, Kaufmann A, Exley R, Deltheil T, et al. LRRK2 BAC transgenic rats develop progressive, L-DOPA-responsive motor impairment, and deficits in dopamine circuit function. Hum Mol Genet. 2016;25:951-63 pubmed publisher
    Mutations in leucine-rich repeat kinase 2 (LRRK2) lead to late-onset, autosomal dominant Parkinson's disease, characterized by the degeneration of dopamine neurons of the substantia nigra pars compacta, a deficit in dopamine ..
  57. Beilina A, Cookson M. Genes associated with Parkinson's disease: regulation of autophagy and beyond. J Neurochem. 2016;139 Suppl 1:91-107 pubmed publisher
    ..This article is part of a special issue on Parkinson disease. ..
  58. Chia R, Haddock S, Beilina A, Rudenko I, Mamais A, Kaganovich A, et al. Phosphorylation of LRRK2 by casein kinase 1α regulates trans-Golgi clustering via differential interaction with ARHGEF7. Nat Commun. 2014;5:5827 pubmed publisher
    b>LRRK2, a gene relevant to Parkinson's disease, encodes a scaffolding protein with both GTPase and kinase activities...
  59. 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...
  60. Law B, Spain V, Leinster V, Chia R, Beilina A, Cho H, et al. A direct interaction between leucine-rich repeat kinase 2 and specific ?-tubulin isoforms regulates tubulin acetylation. J Biol Chem. 2014;289:895-908 pubmed publisher
    Mutations in LRRK2, encoding the multifunctional protein leucine-rich repeat kinase 2 (LRRK2), are a common cause of Parkinson disease...
  61. Shtilbans A, Choi S, Fowkes M, Khitrov G, Shahbazi M, Ting J, et al. Differential gene expression in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2011;12:250-6 pubmed publisher
    ..In conclusion, there is differential tissue-specific gene expression in patients with ALS relative to MMN and controls. Further studies are necessary to evaluate the identified genes in larger patient groups and different tissues. ..
  62. Boddu R, Hull T, Bolisetty S, Hu X, Moehle M, Daher J, et al. Leucine-rich repeat kinase 2 deficiency is protective in rhabdomyolysis-induced kidney injury. Hum Mol Genet. 2015;24:4078-93 pubmed publisher
    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common known genetic cause of Parkinson's disease, and LRRK2 is also linked to Crohn's and Hansen's disease...
  63. Choi I, Kim B, Byun J, Baik S, Huh Y, Kim J, et al. LRRK2 G2019S mutation attenuates microglial motility by inhibiting focal adhesion kinase. Nat Commun. 2015;6:8255 pubmed publisher
    ..we report that microglia carrying a pathogenic mutation in the Parkinson's disease (PD)-associated gene, G2019S-LRRK2 (GS-Tg microglia), show retarded ADP-induced motility and delayed isolation of injury, compared with non-Tg ..
  64. Stanic J, Mellone M, Cirnaru M, Perez Carrion M, Zianni E, Di Luca M, et al. LRRK2 phosphorylation level correlates with abnormal motor behaviour in an experimental model of levodopa-induced dyskinesias. Mol Brain. 2016;9:53 pubmed publisher
    ..Leucine-rich repeat kinase 2 (LRRK2) mutations account for up to 13 % of familial cases of PD...
  65. Park S, Han S, Choi I, Kim B, Park S, Joe E, et al. Interplay between Leucine-Rich Repeat Kinase 2 (LRRK2) and p62/SQSTM-1 in Selective Autophagy. PLoS ONE. 2016;11:e0163029 pubmed publisher
    ..Leucine-rich repeat kinase 2 (LRRK2), a PD-associated protein kinase, is tightly controlled by autophagy-lysosome degradation as well as by the ..
  66. Daher J, Volpicelli Daley L, Blackburn J, Moehle M, West A. Abrogation of ?-synuclein-mediated dopaminergic neurodegeneration in LRRK2-deficient rats. Proc Natl Acad Sci U S A. 2014;111:9289-94 pubmed publisher
    Missense mutations in the leucine-rich repeat kinase 2 (LRRK2) gene can cause late-onset Parkinson disease...
  67. Stafa K, Trancikova A, Webber P, Glauser L, West A, Moore D. GTPase activity and neuronal toxicity of Parkinson's disease-associated LRRK2 is regulated by ArfGAP1. PLoS Genet. 2012;8:e1002526 pubmed publisher
    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...