Agin-Liebes J, Cortes E, Vonsattel JP, Marder K, Alcalay RN. Movement disorders rounds: a case of missing pathology in a patient with LRRK2 Parkinson’s disease. Parkinsonism Relat Disord. 2020;74:76–7.
Article
PubMed
Google Scholar
Alcalay RN, Mirelman A, Saunders-Pullman R, Tang MX, Mejia Santana H, Raymond D, Roos E, Orbe-Reilly M, Gurevich T, Bar Shira A, Gana Weisz M, Yasinovsky K, Zalis M, Thaler A, Deik A, Barrett MJ, Cabassa J, Groves M, Hunt AL, Lubarr N, San Luciano M, Miravite J, Palmese C, Sachdev R, Sarva H, Severt L, Shanker V, Swan MC, Soto-Valencia J, Johannes B, Ortega R, Fahn S, Cote L, Waters C, Mazzoni P, Ford B, Louis E, Levy O, Rosado L, Ruiz D, Dorovski T, Pauciulo M, Nichols W, Orr-Urtreger A, Ozelius L, Clark L, Giladi N, Bressman S, Marder KS. Parkinson disease phenotype in Ashkenazi Jews with and without LRRK2 G2019S mutations. Mov Disord. 2013;28(14):1966–71.
Article
CAS
PubMed
Google Scholar
Alegre-Abarrategui J, Christian H, Lufino MM, Mutihac R, Venda LL, Ansorge O, Wade-Martins R. LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model. Hum Mol Genet. 2009;18(21):4022–34.
Article
CAS
PubMed
PubMed Central
Google Scholar
Armstrong MJ, Okun MS. Diagnosis and treatment of Parkinson disease: a review. JAMA. 2020;323(6):548–60.
Article
PubMed
Google Scholar
Bajpai B. High capacity vectors. In: Ravi I, Baunthiyal M, Saxena J, editors. Advances in Biotechnology. Berlin: Springer; 2014. p. 1–10.
Google Scholar
Benamer HT, de Silva R. LRRK2 G2019S in the North African population: a review. Eur Neurol. 2010;63(6):321–5.
Article
CAS
PubMed
Google Scholar
Bichler Z, Lim HC, Zeng L, Tan EK. Non-motor and motor features in LRRK2 transgenic mice. PLoS ONE. 2013;8(7):e70249.
Article
CAS
PubMed
PubMed Central
Google Scholar
Chang CR, Blackstone C. Dynamic regulation of mitochondrial fission through modification of the dynamin-related protein Drp1. Ann N Y Acad Sci. 2010;1201:34–9.
Article
CAS
PubMed
PubMed Central
Google Scholar
Chen ML, Wu RM. LRRK 2 gene mutations in the pathophysiology of the ROCO domain and therapeutic targets for Parkinson’s disease: a review. J Biomed Sci. 2018;25(1):52.
Article
PubMed
PubMed Central
CAS
Google Scholar
De Giorgio F, Maduro C, Fisher EMC, Acevedo-Arozena A. Transgenic and physiological mouse models give insights into different aspects of amyotrophic lateral sclerosis. Dis Model Mech. 2019;12(1):dmm037424.
Article
PubMed
PubMed Central
CAS
Google Scholar
Deng X, Dzamko N, Prescott A, Davies P, Liu Q, Yang Q, Lee J-D, Patricelli MP, Nomanbhoy TK, Alessi DR. Characterization of a selective inhibitor of the Parkinson’s disease kinase LRRK2. Nat Chem Biol. 2011;7(4):203–5.
Article
CAS
PubMed
PubMed Central
Google Scholar
Di Fonzo A, Rohe CF, Ferreira J, Chien HF, Vacca L, Stocchi F, Guedes L, Fabrizio E, Manfredi M, Vanacore N, Goldwurm S, Breedveld G, Sampaio C, Meco G, Barbosa E, Oostra BA, Bonifati V, Italian Parkinson Genetics N. A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson’s disease. Lancet. 2005;365(9457):412–5.
Article
PubMed
CAS
Google Scholar
Dranka BP, Gifford A, McAllister D, Zielonka J, Joseph J, O’Hara CL, Stucky CL, Kanthasamy AG, Kalyanaraman B. A novel mitochondrially-targeted apocynin derivative prevents hyposmia and loss of motor function in the leucine-rich repeat kinase 2 (LRRK2(R1441G)) transgenic mouse model of Parkinson’s disease. Neurosci Lett. 2014;583:159–64.
Article
CAS
PubMed
PubMed Central
Google Scholar
Dzamko N, Deak M, Hentati F, Reith AD, Prescott AR, Alessi DR, Nichols RJ. Inhibition of LRRK2 kinase activity leads to dephosphorylation of Ser(910)/Ser(935), disruption of 14-3-3 binding and altered cytoplasmic localization. Biochem J. 2010;430(3):405–13.
Article
CAS
PubMed
Google Scholar
Fan TS, Wu RM, Chen PL, Chen TF, Li HY, Lin YH, Chen CY, Chen ML, Tai CH, Lin HI, Lin CH. Clinical heterogeneity of LRRK2 p.I2012T mutation. Parkinsonism Relat Disord. 2016;33:36–43.
Article
PubMed
Google Scholar
Gaig C, Marti MJ, Ezquerra M, Rey MJ, Cardozo A, Tolosa E. G2019S LRRK2 mutation causing Parkinson’s disease without Lewy bodies. J Neurol Neurosurg Psychiatry. 2007;78(6):626–8.
Article
PubMed
PubMed Central
Google Scholar
Gao L, Gomez-Garre P, Diaz-Corrales FJ, Carrillo F, Carballo M, Palomino A, Diaz-Martin J, Mejias R, Vime PJ, Lopez-Barneo J, Mir P. Prevalence and clinical features of LRRK2 mutations in patients with Parkinson’s disease in southern Spain. Eur J Neurol. 2009;16(8):957–60.
Article
CAS
PubMed
Google Scholar
Giasson BI, Covy JP, Bonini NM, Hurtig HI, Farrer MJ, Trojanowski JQ, Van Deerlin VM. Biochemical and pathological characterization of Lrrk2. Ann Neurol. 2006;59(2):315–22.
Article
CAS
PubMed
Google Scholar
Gilks WP, Abou-Sleiman PM, Gandhi S, Jain S, Singleton A, Lees AJ, Shaw K, Bhatia KP, Bonifati V, Quinn NP, Lynch J, Healy DG, Holton JL, Revesz T, Wood NW. A common LRRK2 mutation in idiopathic Parkinson’s disease. Lancet. 2005;365(9457):415–6.
CAS
PubMed
Google Scholar
Goodwin LO, Splinter E, Davis TL, Urban R, He H, Braun RE, Chesler EJ, Kumar V, van Min M, Ndukum J, Philip VM, Reinholdt LG, Svenson K, White JK, Sasner M, Lutz C, Murray SA. Large-scale discovery of mouse transgenic integration sites reveals frequent structural variation and insertional mutagenesis. Genome Res. 2019;29(3):494–505.
Article
CAS
PubMed
PubMed Central
Google Scholar
Gorostidi A, Ruiz-Martinez J, Lopez de Munain A, Alzualde A, Marti Masso JF. LRRK2 G2019S and R1441G mutations associated with Parkinson’s disease are common in the Basque Country, but relative prevalence is determined by ethnicity. Neurogenetics. 2009;10(2):157–9.
Article
CAS
PubMed
Google Scholar
Guiler W, Koehler A, Boykin C, Lu Q. Pharmacological modulators of small GTPases of rho family in neurodegenerative diseases. Front Cell Neurosci. 2021;15:661612.
Article
CAS
PubMed
PubMed Central
Google Scholar
Guo L, Gandhi PN, Wang W, Petersen RB, Wilson-Delfosse AL, Chen SG. The Parkinson’s disease-associated protein, leucine-rich repeat kinase 2 (LRRK2), is an authentic GTPase that stimulates kinase activity. Exp Cell Res. 2007;313(16):3658–70.
Article
CAS
PubMed
PubMed Central
Google Scholar
Healy DG, Falchi M, O’Sullivan SS, Bonifati V, Durr A, Bressman S, Brice A, Aasly J, Zabetian CP, Goldwurm S, Ferreira JJ, Tolosa E, Kay DM, Klein C, Williams DR, Marras C, Lang AE, Wszolek ZK, Berciano J, Schapira AH, Lynch T, Bhatia KP, Gasser T, Lees AJ, Wood NW, International L.C. Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson’s disease: a case–control study. Lancet Neurol. 2008;7(7):583–90.
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, Sassi SB, Yahmed SB, El Euch-Fayeche G, Matthews PM, Middleton LT, Gibson RA, Hentati F, Farrer MJ. LRRK2 Gly2019Ser penetrance in Arab-Berber patients from Tunisia: a case-control genetic study. Lancet Neurol. 2008;7(7):591–4.
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, Griffith A, Hattori N, Leppert D, Watts R, Zabetian CP, Foroud TM, Farrer MJ, Brice A, Middleton L, Hentati F. Clinical features of Parkinson disease patients with homozygous leucine-rich repeat kinase 2 G2019S mutations. Arch Neurol. 2006;63(9):1250–4.
Article
PubMed
Google Scholar
Kachergus J, Mata IF, Hulihan M, Taylor JP, Lincoln S, Aasly J, Gibson JM, Ross OA, Lynch T, Wiley J, Payami H, Nutt J, Maraganore DM, Czyzewski K, Styczynska M, Wszolek ZK, Farrer MJ, Toft M. 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(4):672–80.
Article
CAS
PubMed
PubMed Central
Google Scholar
Khan NL, Jain S, Lynch JM, Pavese N, Abou-Sleiman P, Holton JL, Healy DG, Gilks WP, Sweeney MG, Ganguly M, Gibbons V, Gandhi S, Vaughan J, Eunson LH, Katzenschlager R, Gayton J, Lennox G, Revesz T, Nicholl D, Bhatia KP, Quinn N, Brooks D, Lees AJ, Davis MB, Piccini P, Singleton AB, Wood NW. Mutations in the gene LRRK2 encoding dardarin (PARK8) cause familial Parkinson’s disease: clinical, pathological, olfactory and functional imaging and genetic data. Brain. 2005;128(Pt 12):2786–96.
Article
PubMed
Google Scholar
Lewis PA, Greggio E, Beilina A, Jain S, Baker A, Cookson MR. The R1441C mutation of LRRK2 disrupts GTP hydrolysis. Biochem Biophys Res Commun. 2007;357(3):668–71.
Article
CAS
PubMed
PubMed Central
Google Scholar
Li JQ, Tan L, Yu JT. The role of the LRRK2 gene in Parkinsonism. Mol Neurodegener. 2014;9:47.
Article
CAS
PubMed
PubMed Central
Google Scholar
Li X, Patel JC, Wang J, Avshalumov MV, Nicholson C, Buxbaum JD, Elder GA, Rice ME, Yue Z. Enhanced striatal dopamine transmission and motor performance with LRRK2 overexpression in mice is eliminated by familial Parkinson’s disease mutation G2019S. J Neurosci. 2010;30(5):1788–97.
Article
CAS
PubMed
PubMed Central
Google Scholar
Li X, Tan YC, Poulose S, Olanow CW, Huang XY, Yue Z. Leucine-rich repeat kinase 2 (LRRK2)/PARK8 possesses GTPase activity that is altered in familial Parkinson’s disease R1441C/G mutants. J Neurochem. 2007;103(1):238–47.
CAS
PubMed
PubMed Central
Google Scholar
Li Y, Liu W, Oo TF, Wang L, Tang Y, Jackson-Lewis V, Zhou C, Geghman K, Bogdanov M, Przedborski S, Beal MF, Burke RE, Li C. Mutant LRRK2(R1441G) BAC transgenic mice recapitulate cardinal features of Parkinson’s disease. Nat Neurosci. 2009;12(7):826–8.
Article
CAS
PubMed
PubMed Central
Google Scholar
Lin CH, Tzen KY, Yu CY, Tai CH, Farrer MJ, Wu RM. LRRK2 mutation in familial Parkinson’s disease in a Taiwanese population: clinical, PET, and functional studies. J Biomed Sci. 2008;15(5):661–7.
Article
PubMed
Google Scholar
Liu HF, Ho PW, Leung GC, Lam CS, Pang SY, Li L, Kung MH, Ramsden DB, Ho SL. Combined LRRK2 mutation, aging and chronic low dose oral rotenone as a model of Parkinson’s disease. Sci Rep. 2017;7:40887.
Article
CAS
PubMed
PubMed Central
Google Scholar
Liu HF, Lu S, Ho PW, Tse HM, Pang SY, Kung MH, Ho JW, Ramsden DB, Zhou ZJ, Ho SL. LRRK2 R1441G mice are more liable to dopamine depletion and locomotor inactivity. Ann Clin Transl Neurol. 2014;1(3):199–208.
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. Neuropathology of Parkinson’s disease with the R1441G mutation in LRRK2. Mov Disord. 2009;24(13):1998–2001.
Article
PubMed
Google Scholar
Mirelman A, Bonato P, Camicioli R, Ellis TD, Giladi N, Hamilton JL, Hass CJ, Hausdorff JM, Pelosin E, Almeida QJ. Gait impairments in Parkinson’s disease. Lancet Neurol. 2019;18(7):697–708.
Article
PubMed
Google Scholar
Morfini G, Pigino G, Opalach K, Serulle Y, Moreira JE, Sugimori M, Llinas RR, Brady ST. 1-Methyl-4-phenylpyridinium affects fast axonal transport by activation of caspase and protein kinase C. Proc Natl Acad Sci USA. 2007;104(7):2442–7.
Article
CAS
PubMed
PubMed Central
Google Scholar
Nichols RJ, Dzamko N, Morrice NA, Campbell DG, Deak M, Ordureau A, Macartney T, Tong Y, Shen J, Prescott AR, Alessi DR. 14-3-3 binding to LRRK2 is disrupted by multiple Parkinson’s disease-associated mutations and regulates cytoplasmic localization. Biochem J. 2010;430(3):393–404.
Article
CAS
PubMed
Google Scholar
Nichols WC, Pankratz N, Hernandez D, Paisan-Ruiz C, Jain S, Halter CA, Michaels VE, Reed T, Rudolph A, Shults CW, Singleton A, Foroud T, Parkinson Study Group P.i. Genetic screening for a single common LRRK2 mutation in familial Parkinson’s disease. Lancet. 2005;365(9457):410–2.
CAS
PubMed
Google Scholar
Niu J, Yu M, Wang C, Xu Z. Leucine-rich repeat kinase 2 disturbs mitochondrial dynamics via Dynamin-like protein. J Neurochem. 2012;122(3):650–8.
Article
CAS
PubMed
Google Scholar
Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, Obeso J, Marek K, Litvan I, Lang AE, Halliday G, Goetz CG, Gasser T, Dubois B, Chan P, Bloem BR, Adler CH, Deuschl G. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord. 2015;30(12):1591–601.
Article
PubMed
Google Scholar
Ramonet D, Daher JP, Lin BM, Stafa K, Kim J, Banerjee R, Westerlund M, Pletnikova O, Glauser L, Yang L, Liu Y, Swing DA, Beal MF, Troncoso JC, McCaffery JM, Jenkins NA, Copeland NG, Galter D, Thomas B, Lee MK, Dawson TM, Dawson VL, Moore DJ. Dopaminergic neuronal loss, reduced neurite complexity and autophagic abnormalities in transgenic mice expressing G2019S mutant LRRK2. PLoS ONE. 2011;6(4):e18568.
Article
CAS
PubMed
PubMed Central
Google Scholar
Rideout HJ. Neuronal death signaling pathways triggered by mutant LRRK2. Biochem Soc Trans. 2017;45(1):123–9.
Article
CAS
PubMed
Google Scholar
Saha AR, Hill J, Utton MA, Asuni AA, Ackerley S, Grierson AJ, Miller CC, Davies AM, Buchman VL, Anderton BH, Hanger DP. Parkinson’s disease alpha-synuclein mutations exhibit defective axonal transport in cultured neurons. J Cell Sci. 2004;117(Pt 7):1017–24.
Article
CAS
PubMed
Google Scholar
Santos D, Esteves AR, Silva DF, Januario C, Cardoso SM. The impact of mitochondrial fusion and fission modulation in sporadic Parkinson’s disease. Mol Neurobiol. 2015;52(1):573–86.
Article
CAS
PubMed
Google Scholar
Seibenhener ML, Wooten MC. Use of the Open Field Maze to measure locomotor and anxiety-like behavior in mice. J Vis Exp. 2015;(96):e52434.
Sheng Z, Zhang S, Bustos D, Kleinheinz T, Le Pichon CE, Dominguez SL, Solanoy HO, Drummond J, Zhang X, Ding X, Cai F, Song Q, Li X, Yue Z, van der Brug MP, Burdick DJ, Gunzner-Toste J, Chen H, Liu X, Estrada AA, Sweeney ZK, Scearce-Levie K, Moffat JG, Kirkpatrick DS, Zhu H. Ser1292 autophosphorylation is an indicator of LRRK2 kinase activity and contributes to the cellular effects of PD mutations. Sci Transl Med. 2012;4(164):164ra161.
Article
PubMed
CAS
Google Scholar
Simon-Sanchez J, Marti-Masso JF, Sanchez-Mut JV, Paisan-Ruiz C, Martinez-Gil A, Ruiz-Martinez J, Saenz A, Singleton AB, Lopez de Munain A, Perez-Tur J. Parkinson’s disease due to the R1441G mutation in Dardarin: a founder effect in the Basques. Mov Disord. 2006;21(11):1954–9.
Article
PubMed
Google Scholar
Steger M, Tonelli F, Ito G, Davies P, Trost M, Vetter M, Wachter S, Lorentzen E, Duddy G, Wilson S, Baptista MA, Fiske BK, Fell MJ, Morrow JA, Reith AD, Alessi DR, Mann M. Phosphoproteomics reveals that Parkinson’s disease kinase LRRK2 regulates a subset of Rab GTPases. Elife. 2016;5:e12813.
Article
PubMed
PubMed Central
Google Scholar
Su YC, Qi X. Inhibition of excessive mitochondrial fission reduced aberrant autophagy and neuronal damage caused by LRRK2 G2019S mutation. Hum Mol Genet. 2013;22(22):4545–61.
Article
CAS
PubMed
Google Scholar
Tan EK, Peng R, Wu YR, Wu RM, Wu-Chou YH, Tan LC, An XK, Chen CM, Fook-Chong S, Lu CS. LRRK2 G2385R modulates age at onset in Parkinson’s disease: a multi-center pooled analysis. Am J Med Genet B Neuropsychiatr Genet. 2009;150B(7):1022–3.
Article
CAS
PubMed
Google Scholar
Tanaka S, Young JW, Halberstadt AL, Masten VL, Geyer MA. Four factors underlying mouse behavior in an open field. Behav Brain Res. 2012;233(1):55–61.
Article
PubMed
Google Scholar
Tolosa E, Vila M, Klein C, Rascol O. LRRK2 in Parkinson disease: challenges of clinical trials. Nat Rev Neurol. 2020;16(2):97–107.
Article
PubMed
Google Scholar
Tong Y, Pisani A, Martella G, Karouani M, Yamaguchi H, Pothos EN, Shen J. R1441C mutation in LRRK2 impairs dopaminergic neurotransmission in mice. Proc Natl Acad Sci USA. 2009;106(34):14622–7.
Article
CAS
PubMed
PubMed Central
Google Scholar
Tong Y, Yamaguchi H, Giaime E, Boyle S, Kopan R, Kelleher RJ 3rd, Shen J. 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 USA. 2010;107(21):9879–84.
Article
CAS
PubMed
PubMed Central
Google Scholar
Vinagre-Aragon A, Campo-Caballero D, Mondragon-Rezola E, Pardina-Vilella L, Hernandez EH, Gorostidi A, Croitoru I, Bergareche A, Ruiz-Martinez J. A more homogeneous phenotype in Parkinson’s disease related to R1441G mutation in the LRRK2 Gene. Front Neurol. 2021;12:635396.
Article
PubMed
PubMed Central
Google Scholar
Volta M, Melrose H. LRRK2 mouse models: dissecting the behavior, striatal neurochemistry and neurophysiology of PD pathogenesis. Biochem Soc Trans. 2017;45(1):113–22.
Article
CAS
PubMed
Google Scholar
Wang X, Yan MH, Fujioka H, Liu J, Wilson-Delfosse A, Chen SG, Perry G, Casadesus G, Zhu X. LRRK2 regulates mitochondrial dynamics and function through direct interaction with DLP1. Hum Mol Genet. 2012;21(9):1931–44.
Article
CAS
PubMed
PubMed Central
Google Scholar
Willard AM, Bouchard RS, Gittis AH. Differential degradation of motor deficits during gradual dopamine depletion with 6-hydroxydopamine in mice. Neuroscience. 2015;301:254–67.
Article
CAS
PubMed
Google Scholar
Xiong Y, Dawson TM, Dawson VL. Models of LRRK2-associated Parkinson’s disease. Adv Neurobiol. 2017;14:163–91.
Article
PubMed
PubMed Central
Google Scholar
Yang X.W. and Gong S. An overview on the generation of BAC transgenic mice for neuroscience research. Curr Protoc Neurosci. 2005; Chapter 5:Unit 5 20.
Yue M, Hinkle KM, Davies P, Trushina E, Fiesel FC, Christenson TA, Schroeder AS, Zhang L, Bowles E, Behrouz B, Lincoln SJ, Beevers JE, Milnerwood AJ, Kurti A, McLean PJ, Fryer JD, Springer W, Dickson DW, Farrer MJ, Melrose HL. Progressive dopaminergic alterations and mitochondrial abnormalities in LRRK2 G2019S knock-in mice. Neurobiol Dis. 2015;78:172–95.
Article
CAS
PubMed
PubMed Central
Google Scholar
Zhao Y, Keshiya S, Atashrazm F, Gao J, Ittner LM, Alessi DR, Halliday GM, Fu Y, Dzamko N. Nigrostriatal pathology with reduced astrocytes in LRRK2 S910/S935 phosphorylation deficient knockin mice. Neurobiol Dis. 2018;120:76–87.
Article
CAS
PubMed
PubMed Central
Google Scholar