Alcalay RN, Mirelman A, Saunders-Pullman R, Tang MX, Mejia Santana H, Raymond D, Roos E, Orbe-Reilly M, Gurevich T, Bar Shira A et al (2013, 1966) Parkinson disease phenotype in Ashkenazi Jews with and without LRRK2 G2019S mutations. Mov Disord 28:–1971. https://doi.org/10.1002/mds.25647
Article
CAS
PubMed
Google Scholar
Bolger AM, Lohse M, Usadel B (2014) Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30:2114–2120. https://doi.org/10.1093/bioinformatics/btu170
Article
CAS
PubMed
PubMed Central
Google Scholar
Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239–259
Article
CAS
PubMed
Google Scholar
Chandra S, Chen X, Rizo J, Jahn R, Sudhof TC (2003) A broken alpha -helix in folded alpha -Synuclein. J Biol Chem 278:15313–15318. https://doi.org/10.1074/jbc.M213128200
Article
CAS
PubMed
Google Scholar
Cherra SJ 3rd, Steer E, Gusdon AM, Kiselyov K, Chu CT (2013) Mutant LRRK2 elicits calcium imbalance and depletion of dendritic mitochondria in neurons. Am J Pathol 182:474–484. https://doi.org/10.1016/j.ajpath.2012.10.027
Article
CAS
PubMed
PubMed Central
Google Scholar
Crary JF, Trojanowski JQ, Schneider JA, Abisambra JF, Abner EL, Alafuzoff I, Arnold SE, Attems J, Beach TG, Bigio EH et al (2014) Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol 128:755–766. https://doi.org/10.1007/s00401-014-1349-0
Article
CAS
PubMed
PubMed Central
Google Scholar
Deng H, Wang P, Jankovic J (2018) The genetics of Parkinson disease. Ageing Res Rev 42:72–85. https://doi.org/10.1016/j.arr.2017.12.007
Article
CAS
PubMed
Google Scholar
Di Fonzo A, Wu-Chou YH, Lu CS, van Doeselaar M, Simons EJ, Rohe CF, Chang HC, Chen RS, Weng YH, Vanacore N et al (2006) A common missense variant in the LRRK2 gene, Gly2385Arg, associated with Parkinson's disease risk in Taiwan. Neurogenetics 7:133–138. https://doi.org/10.1007/s10048-006-0041-5
Article
CAS
PubMed
Google Scholar
Dickson DW (2018) Neuropathology of Parkinson disease. Parkinsonism Relat Disord 46(Suppl 1):S30–S33. https://doi.org/10.1016/j.parkreldis.2017.07.033
Article
PubMed
Google Scholar
Doherty KM, Hardy J (2013) Parkin disease and the Lewy body conundrum. Mov Disord 28:702–704. https://doi.org/10.1002/mds.25486
Article
PubMed
PubMed Central
Google Scholar
Ferree A, Shirihai O (2012) Mitochondrial dynamics: the intersection of form and function. Adv Exp Med Biol 748:13–40. https://doi.org/10.1007/978-1-4614-3573-0_2
Article
CAS
PubMed
PubMed Central
Google Scholar
Ferreira JJ, Guedes LC, Rosa MM, Coelho M, van Doeselaar M, Schweiger D, Di Fonzo A, Oostra BA, Sampaio C, Bonifati V (2007) High prevalence of LRRK2 mutations in familial and sporadic Parkinson’s disease in Portugal. Mov Disord 22:1194–1201. https://doi.org/10.1002/mds.21525
Article
PubMed
Google Scholar
Funayama M, Hasegawa K, Kowa H, Saito M, Tsuji S, Obata F (2002) A new locus for Parkinson's disease (PARK8) maps to chromosome 12p11.2-q13.1. Ann Neurol 51:296–301
Article
CAS
PubMed
Google Scholar
Funayama M, Li Y, Tomiyama H, Yoshino H, Imamichi Y, Yamamoto M, Murata M, Toda T, Mizuno Y, Hattori N (2007) Leucine-rich repeat kinase 2 G2385R variant is a risk factor for Parkinson disease in Asian population. Neuroreport 18:273–275. https://doi.org/10.1097/WNR.0b013e32801254b6
Article
CAS
PubMed
Google Scholar
Gaig C, Marti MJ, Ezquerra M, Rey MJ, Cardozo A, Tolosa E (2007) G2019S LRRK2 mutation causing Parkinson's disease without Lewy bodies. J Neurol Neurosurg Psychiatry 78:626–628. https://doi.org/10.1136/jnnp.2006.107904
Article
PubMed
PubMed Central
Google Scholar
Gao Y, Wilson GR, Stephenson SEM, Bozaoglu K, Farrer MJ, Lockhart PJ (2018) The emerging role of Rab GTPases in the pathogenesis of Parkinson's disease. Mov Disord 33:196–207. https://doi.org/10.1002/mds.27270
Article
CAS
PubMed
Google Scholar
Giasson BI, Covy JP, Bonini NM, Hurtig HI, Farrer MJ, Trojanowski JQ, Van Deerlin VM (2006) Biochemical and pathological characterization of Lrrk2. Ann Neurol 59:315–322. https://doi.org/10.1002/ana.20791
Article
CAS
PubMed
Google Scholar
Gibb WR, Lees AJ (1988) The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. J Neurol Neurosurg Psychiatry 51:745–752
Article
CAS
PubMed Central
PubMed
Google Scholar
Hasegawa K, Stoessl AJ, Yokoyama T, Kowa H, Wszolek ZK, Yagishita S (2009) Familial parkinsonism: study of original Sagamihara PARK8 (I2020T) kindred with variable clinicopathologic outcomes. Parkinsonism Relat Disord 15:300–306. https://doi.org/10.1016/j.parkreldis.2008.07.010
Article
PubMed
Google Scholar
Haugarvoll K, Rademakers R, Kachergus JM, Nuytemans K, Ross OA, Gibson JM, Tan EK, Gaig C, Tolosa E, Goldwurm S et al (2008) Lrrk2 R1441C parkinsonism is clinically similar to sporadic Parkinson disease. Neurology 70:1456–1460. https://doi.org/10.1212/01.wnl.0000304044.22253.03
Article
CAS
PubMed
Google Scholar
Healy DG, Falchi M, O'Sullivan SS, Bonifati V, Durr A, Bressman S, Brice A, Aasly J, Zabetian CP, Goldwurm S et al (2008) Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson’s disease: a case-control study. Lancet Neurol 7:583–590. https://doi.org/10.1016/s1474-4422(08)70117-0
Article
CAS
PubMed
PubMed Central
Google Scholar
Herzig MC, Kolly C, Persohn E, Theil D, Schweizer T, Hafner T, Stemmelen C, Troxler TJ, Schmid P, Danner S et al (2011) LRRK2 protein levels are determined by kinase function and are crucial for kidney and lung homeostasis in mice. Hum Mol Genet 20:4209–4223. https://doi.org/10.1093/hmg/ddr348
Article
CAS
PubMed
PubMed Central
Google Scholar
Hindle SJ, Elliott CJ (2013) Spread of neuronal degeneration in a dopaminergic, Lrrk-G2019S model of Parkinson disease. Autophagy 9:936–938. https://doi.org/10.4161/auto.24397
Article
CAS
PubMed
PubMed Central
Google Scholar
Hulihan MM, Ishihara-Paul L, Kachergus J, Warren L, Amouri R, Elango R, Prinjha RK, Upmanyu R, Kefi M, Zouari M et al (2008) LRRK2 Gly2019Ser penetrance in Arab-Berber patients from Tunisia: a case-control genetic study. Lancet Neurol 7:591–594. https://doi.org/10.1016/s1474-4422(08)70116-9
Article
CAS
PubMed
Google Scholar
Ishihara L, Warren L, Gibson R, Amouri R, Lesage S, Durr A, Tazir M, Wszolek ZK, Uitti RJ, Nichols WC et al (2006) Clinical features of Parkinson disease patients with homozygous leucine-rich repeat kinase 2 G2019S mutations. Arch Neurol 63:1250–1254. https://doi.org/10.1001/archneur.63.9.1250
Article
PubMed
Google Scholar
Islam MS, Moore DJ (2017) Mechanisms of LRRK2-dependent neurodegeneration: role of enzymatic activity and protein aggregation. Biochem Soc Trans 45:163–172. https://doi.org/10.1042/BST20160264
Article
CAS
PubMed
PubMed Central
Google Scholar
Li H, Durbin R (2009) Fast and accurate short read alignment with burrows-wheeler transform. Bioinformatics 25:1754–1760. https://doi.org/10.1093/bioinformatics/btp324
Article
CAS
PubMed
PubMed Central
Google Scholar
Manzoni C, Mamais A, Dihanich S, Abeti R, Soutar MPM, Plun-Favreau H, Giunti P, Tooze SA, Bandopadhyay R, Lewis PA (2013) Inhibition of LRRK2 kinase activity stimulates macroautophagy. Biochim Biophys Acta 1833:2900–2910. https://doi.org/10.1016/j.bbamcr.2013.07.020
Article
CAS
PubMed
PubMed Central
Google Scholar
Marti-Masso JF, Ruiz-Martinez J, Bolano MJ, Ruiz I, Gorostidi A, Moreno F, Ferrer I, Lopez de Munain A (2009) Neuropathology of Parkinson’s disease with the R1441G mutation in LRRK2. Mov Disord 24:1998–2001. https://doi.org/10.1002/mds.22677
Article
PubMed
Google Scholar
Mata IF, Kachergus JM, Taylor JP, Lincoln S, Aasly J, Lynch T, Hulihan MM, Cobb SA, Wu RM, Lu CS et al (2005) Lrrk2 pathogenic substitutions in Parkinson’s disease. Neurogenetics 6:171–177. https://doi.org/10.1007/s10048-005-0005-1
Article
CAS
PubMed
Google Scholar
McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S, Daly M et al (2010) The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 20:1297–1303. https://doi.org/10.1101/gr.107524.110
Article
CAS
PubMed
PubMed Central
Google Scholar
Orenstein SJ, Kuo SH, Tasset I, Arias E, Koga H, Fernandez-Carasa I, Cortes E, Honig LS, Dauer W, Consiglio A et al (2013) Interplay of LRRK2 with chaperone-mediated autophagy. Nat Neurosci 16:394–406. https://doi.org/10.1038/nn.3350
Article
CAS
PubMed
PubMed Central
Google Scholar
Paisan-Ruiz C, Jain S, Evans EW, Gilks WP, Simon J, van der Brug M, Lopez de Munain A, Aparicio S, Gil AM, Khan N et al (2004) Cloning of the gene containing mutations that cause PARK8-linked Parkinson’s disease. Neuron 44:595–600. https://doi.org/10.1016/j.neuron.2004.10.023
Article
CAS
PubMed
Google Scholar
Paisan-Ruiz C, Lewis PA, Singleton AB (2013) LRRK2: cause, risk, and mechanism. J Parkinsons Dis 3:85–103. https://doi.org/10.3233/JPD-130192
Article
CAS
PubMed
PubMed Central
Google Scholar
Purlyte E, Dhekne HS, Sarhan AR, Gomez R, Lis P, Wightman M, Martinez TN, Tonelli F, Pfeffer SR, Alessi DR (2018) Rab29 activation of the Parkinson’s disease-associated LRRK2 kinase. EMBO J 37:1–18. https://doi.org/10.15252/embj.201798099
Article
CAS
PubMed
Google Scholar
Rajput A, Dickson DW, Robinson CA, Ross OA, Dachsel JC, Lincoln SJ, Cobb SA, Rajput ML, Farrer MJ (2006) Parkinsonism, Lrrk2 G2019S, and tau neuropathology. Neurology 67:1506–1508. https://doi.org/10.1212/01.wnl.0000240220.33950.0c
Article
CAS
PubMed
Google Scholar
Ramonet D, Daher JP, Lin BM, Stafa K, Kim J, Banerjee R, Westerlund M, Pletnikova O, Glauser L, Yang L et al (2011) Dopaminergic neuronal loss, reduced neurite complexity and autophagic abnormalities in transgenic mice expressing G2019S mutant LRRK2. PLoS One 6:e18568. https://doi.org/10.1371/journal.pone.0018568
Article
CAS
PubMed
PubMed Central
Google Scholar
Ross OA, Toft M, Whittle AJ, Johnson JL, Papapetropoulos S, Mash DC, Litvan I, Gordon MF, Wszolek ZK, Farrer MJ et al (2006) Lrrk2 and Lewy body disease. Ann Neurol 59:388–393. https://doi.org/10.1002/ana.20731
Article
CAS
PubMed
Google Scholar
Schapansky J, Nardozzi JD, Felizia F, LaVoie MJ (2014) Membrane recruitment of endogenous LRRK2 precedes its potent regulation of autophagy. Hum Mol Genet 23:4201–4214. https://doi.org/10.1093/hmg/ddu138
Article
CAS
PubMed
PubMed Central
Google Scholar
Schneider SA, Alcalay RN (2017) Neuropathology of genetic synucleinopathies with parkinsonism: review of the literature. Mov Disord 32:1504–1523. https://doi.org/10.1002/mds.27193
Article
PubMed
PubMed Central
Google Scholar
Smith WW, Pei Z, Jiang H, Dawson VL, Dawson TM, Ross CA (2006) Kinase activity of mutant LRRK2 mediates neuronal toxicity. Nat Neurosci 9:1231–1233. https://doi.org/10.1038/nn1776
Article
CAS
PubMed
Google Scholar
Spanaki C, Latsoudis H, Plaitakis A (2006) LRRK2 mutations on Crete: R1441H associated with PD evolving to PSP. Neurology 67:1518–1519. https://doi.org/10.1212/01.wnl.0000239829.33936.73
Article
PubMed
Google Scholar
Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997) Alpha-synuclein in Lewy bodies. Nature 388:839–840. https://doi.org/10.1038/42166
Article
CAS
PubMed
Google Scholar
Stolz A, Dikic I (2014) PINK1-PARKIN interplay: down to ubiquitin phosphorylation. Mol Cell 56:341–342. https://doi.org/10.1016/j.molcel.2014.10.022
Article
CAS
PubMed
Google Scholar
Takanashi M, Li Y, Hattori N (2016) Absence of Lewy pathology associated with PINK1 homozygous mutation. Neurology 86:2212–2213. https://doi.org/10.1212/wnl.0000000000002744
Article
PubMed
Google Scholar
Tan EK, Zhao Y, Skipper L, Tan MG, Di Fonzo A, Sun L, Fook-Chong S, Tang S, Chua E, Yuen Y et al (2007) The LRRK2 Gly2385Arg variant is associated with Parkinson's disease: genetic and functional evidence. Hum Genet 120:857–863. https://doi.org/10.1007/s00439-006-0268-0
Article
CAS
PubMed
Google Scholar
Tong Y, Giaime E, Yamaguchi H, Ichimura T, Liu Y, Si H, Cai H, Bonventre JV, Shen J (2012) Loss of leucine-rich repeat kinase 2 causes age-dependent bi-phasic alterations of the autophagy pathway. Mol Neurodegener 7:2. https://doi.org/10.1186/1750-1326-7-2
Article
CAS
PubMed
PubMed Central
Google Scholar
Tong Y, Pisani A, Martella G, Karouani M, Yamaguchi H, Pothos EN, Shen J (2009) R1441C mutation in LRRK2 impairs dopaminergic neurotransmission in mice. Proc Natl Acad Sci U S A 106:14622–14627. https://doi.org/10.1073/pnas.0906334106
Article
PubMed
PubMed Central
Google Scholar
Wang K, Li M, Hakonarson H (2010) ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 38:e164. https://doi.org/10.1093/nar/gkq603
Article
CAS
PubMed
PubMed Central
Google Scholar
West AB, Moore DJ, Biskup S, Bugayenko A, Smith WW, Ross CA, Dawson VL, Dawson TM (2005) Parkinson’s disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc Natl Acad Sci U S A 102:16842–16847. https://doi.org/10.1073/pnas.0507360102
Article
CAS
PubMed
PubMed Central
Google Scholar
Xiong Y, Coombes CE, Kilaru A, Li X, Gitler AD, Bowers WJ, Dawson VL, Dawson TM, Moore DJ (2010) GTPase activity plays a key role in the pathobiology of LRRK2. PLoS Genet 6:e1000902. https://doi.org/10.1371/journal.pgen.1000902
Article
CAS
PubMed
PubMed Central
Google Scholar
Yakhine-Diop SM, Bravo-San Pedro JM, Gomez-Sanchez R, Pizarro-Estrella E, Rodriguez-Arribas M, Climent V, Aiastui A, Lopez de Munain A, Fuentes JM, Gonzalez-Polo RA (2014) G2019S LRRK2 mutant fibroblasts from Parkinson’s disease patients show increased sensitivity to neurotoxin 1-methyl-4-phenylpyridinium dependent of autophagy. Toxicology 324:1–9. https://doi.org/10.1016/j.tox.2014.07.001
Article
CAS
PubMed
Google Scholar
Zabetian CP, Samii A, Mosley AD, Roberts JW, Leis BC, Yearout D, Raskind WH, Griffith A (2005) A clinic-based study of the LRRK2 gene in Parkinson disease yields new mutations. Neurology 65:741–744. https://doi.org/10.1212/01.wnl.0000172630.22804.73
Article
CAS
PubMed
Google Scholar
Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, Kachergus J, Hulihan M, Uitti RJ, Calne DB et al (2004) Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44:601–607. https://doi.org/10.1016/j.neuron.2004.11.005
Article
CAS
PubMed
Google Scholar