title: Models for LRRK2-Linked Parkinsonism.
abstract: Parkinson's disease (PD) is a progressive neurodegenerative movement disorder characterized by the selective loss of dopaminergic neurons and the presence of Lewy bodies. The pathogenesis of PD is not fully understood, but it appears to involve both genetic susceptibility and environmental factors. Treatment for PD that prevents neuronal death progression in the dopaminergic system and abnormal protein deposition in the brain is not yet available. Recently, mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been identified to cause autosomal-dominant late-onset PD and contribute to sporadic PD. Here, we review the recent models for LRRK2-linked Parkinsonism and their utility in studying LRRK2 neurobiology, pathogenesis, and potential therapeutics.
authors: Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA.
authors: Tianxia
authors: T
authors: Li
authors: Dejun
authors: D
authors: Yang
authors: Sarah
authors: S
authors: Sushchky
authors: Zhaohui
authors: Z
authors: Liu
authors: Wanli W
authors: WW
authors: Smith
references: Biol Cell. 2009 Mar;101(3):183-91
references: 19152505
references: PLoS One. 2009 Jun 17;4(6):e5949
references: 19536328
references: Neurology. 2002 Jan 22;58(2):179-85
references: 11805242
references: J Neurosci. 2010 Dec 15;30(50):16959-69
references: 21159966
references: Lancet. 2005 Jan 29-Feb 4;365(9457):410-2
references: 15680455
references: Parkinsonism Relat Disord. 2007 Oct;13(7):382-5
references: 17400507
references: Proc Natl Acad Sci U S A. 2006 Jul 11;103(28):10793-8
references: 16818890
references: PLoS Genet. 2010 Apr 22;6(4):e1000914
references: 20421934
references: FEBS J. 2009 Nov;276(22):6436-44
references: 19804415
references: Science. 2003 Oct 31;302(5646):819-22
references: 14593166
references: Brain Res. 2007 Jun 25;1155:208-19
references: 17512502
references: PLoS One. 2009 Dec 24;4(12):e8463
references: 20041156
references: Curr Opin Neurol. 2002 Aug;15(4):483-9
references: 12151847
references: Neurology. 2006 Oct 24;67(8):1506-8
references: 17060589
references: J Neurosci. 2008 Mar 26;28(13):3384-91
references: 18367605
references: Ann Med. 2005;37(2):86-96
references: 16026116
references: Ann Neurol. 2005 Jun;57(6):918-21
references: 15880653
references: Ann Neurol. 2006 Apr;59(4):714-9
references: 16532471
references: Lancet. 2005 Jan 29-Feb 4;365(9457):415-6
references: 15680457
references: J Neurosci. 2010 Feb 3;30(5):1788-97
references: 20130188
references: Biochim Biophys Acta. 2003 Dec 7;1643(1-3):5-10
references: 14654223
references: Autophagy. 2009 Nov;5(8):1208-10
references: 19770575
references: Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2897-902
references: 19196961
references: J Neurochem. 2009 Nov;111(3):703-15
references: 19712061
references: Neurobiol Dis. 2010 Dec;40(3):503-17
references: 20659558
references: Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2693-8
references: 18258746
references: Eur J Hum Genet. 2006 Mar;14(3):322-31
references: 16333314
references: J Biol Chem. 2010 Sep 17;285(38):29569-76
references: 20595391
references: Hum Mol Genet. 2007 Sep 1;16(17):2031-9
references: 17584768
references: Nat Neurosci. 2005 May;8(5):657-63
references: 15834418
references: Ann Neurol. 2006 Nov;60(5):557-69
references: 17120249
references: Gene. 2005 Nov 21;361:133-9
references: 16203113
references: Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13670-5
references: 16155123
references: Nat Neurosci. 2009 Jul;12(7):826-8
references: 19503083
references: J Neurochem. 2011 Jan;116(2):304-15
references: 21073465
references: Nat Neurosci. 2006 Oct;9(10):1231-3
references: 16980962
references: Neuron. 2004 Nov 18;44(4):595-600
references: 15541308
references: J Neurosci Res. 2008 Jun;86(8):1711-20
references: 18214993
references: Neurogenetics. 2007 Apr;8(2):95-102
references: 17225181
references: J Biol Chem. 2008 Jun 13;283(24):16906-14
references: 18397888
references: Neuron. 2006 Nov 22;52(4):587-93
references: 17114044
references: J Neurosci. 2009 Jul 22;29(29):9210-8
references: 19625511
references: Hum Mol Genet. 2009 Nov 1;18(21):4022-34
references: 19640926
references: Cell Death Dis. 2010;1:e2
references: 21152247
references: J Neurosci. 2007 Oct 31;27(44):11865-8
references: 17978026
references: Mol Cell Proteomics. 2011 Jan;10(1):M110.001172
references: 20876399
references: Nat Med. 2010 Sep;16(9):998-1000
references: 20729864
references: Neurology. 2005 Sep 13;65(5):738-40
references: 16157908
references: J Neuropathol Exp Neurol. 1996 Mar;55(3):259-72
references: 8786384
references: Hum Mol Genet. 2009 Nov 15;18(22):4390-404
references: 19692353
references: J Neurochem. 2008 May;105(3):1048-56
references: 18182054
references: Curr Opin Neurol. 2005 Aug;18(4):363-9
references: 16003110
references: Neuron. 2004 Nov 18;44(4):601-7
references: 15541309
references: J Neurosci. 2009 Dec 16;29(50):15846-50
references: 20016100
references: Nature. 2006 Jun 29;441(7097):1162-6
references: 16672981
references: Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1499-504
references: 18230735
references: Biochem J. 2010 Sep 15;430(3):405-13
references: 20659021
references: Neuroreport. 2007 Feb 12;18(3):273-5
references: 17314670
references: Ann Neurol. 2006 Feb;59(2):315-22
references: 16437584
references: J Neurosci. 2009 Sep 9;29(36):11257-62
references: 19741132
references: Nat Neurosci. 2009 Sep;12(9):1129-35
references: 19684592
references: Nature. 2006 Jun 29;441(7097):1157-61
references: 16672980
references: Neuroreport. 2002 Jul 19;13(10):1279-83
references: 12151787
references: Hum Mol Genet. 2003 Mar 1;12(5):517-26
references: 12588799
references: Curr Opin Neurol. 2007 Aug;20(4):453-64
references: 17620882
references: Neurology. 2005 Sep 13;65(5):696-700
references: 16157901
references: Nature. 2010 Jul 29;466(7306):637-41
references: 20671708
references: Curr Opin Cell Biol. 1995 Feb;7(1):55-64
references: 7755990
references: Ann Neurol. 2006 Nov;60(5):617-8; author reply 618-9
references: 16847950
references: Neurobiol Dis. 2011 Mar;41(3):706-16
references: 21168496
references: J Proteome Res. 2010 Apr 5;9(4):1738-45
references: 20108944
references: Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18676-81
references: 16352719
references: Genome Res. 2001 Jun;11(6):1114-25
references: 11381037
references: Hum Mol Genet. 2006 Jan 15;15(2):223-32
references: 16321986
references: Hum Mol Genet. 2007 Jun 1;16(11):1319-26
references: 17409193
references: Neuron. 2003 Mar 27;37(6):911-24
references: 12670421
references: Development. 2004 May;131(9):2183-94
references: 15073152
references: Nat Rev Neurosci. 2010 Dec;11(12):791-7
references: 21088684
references: Mov Disord. 2006 Sep;21(9):1506-10
references: 16758483
references: Biochem Biophys Res Commun. 2009 Nov 20;389(3):449-54
references: 19733152
references: Biochem J. 2010 Sep 15;430(3):393-404
references: 20642453
references: J Neurochem. 2010 Mar;112(6):1593-604
references: 20067578
references: Lancet. 2005 Jan 29-Feb 4;365(9457):412-5
references: 15680456
references: Hum Mol Genet. 2009 Oct 15;18(20):3955-68
references: 19625296
references: Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14622-7
references: 19667187
references: Neuroscience. 2009 Oct 6;163(2):533-9
references: 19559761
references: EMBO J. 2008 Sep 17;27(18):2432-43
references: 18701920
references: Am J Hum Genet. 2005 Apr;76(4):672-80
references: 15726496
references: J Pathol. 2004 Nov;204(4):438-49
references: 15495240
references: Neurology. 2005 Sep 13;65(5):741-4
references: 16157909
references: Neuron. 2010 Jun 10;66(5):646-61
references: 20547124
references: Biochemistry. 2007 Feb 6;46(5):1380-8
references: 17260967
references: Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4078-83
references: 12642658
references: Neurobiol Dis. 2010 Oct;40(1):73-81
references: 20382224
references: PLoS One. 2010 Jan 15;5(1):e8730
references: 20090955
references: Neuron. 2009 Dec 24;64(6):807-27
references: 20064389
references: Ann Neurol. 2006 Feb;59(2):388-93
references: 16437559
references: Hum Mol Genet. 2007 Jan 15;16(2):223-32
references: 17200152
references: Proc Natl Acad Sci U S A. 2010 May 25;107(21):9879-84
references: 20457918
references: Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16842-7
references: 16269541
references: J Neurochem. 2007 Oct;103(1):238-47
references: 17623048
references: J Neurochem. 2007 May;101(4):906-17
references: 17250651
references: Exp Cell Res. 2007 Oct 1;313(16):3658-70
references: 17706965
references: J Neurochem. 2006 Aug;98(3):951-61
references: 16771836
references: Neurodegener Dis. 2006;3(6):338-56
references: 17192723
references: Ann Neurol. 2005 Jun;57(6):933-4
references: 15929036
references: Curr Opin Struct Biol. 2001 Dec;11(6):725-32
references: 11751054
references: Curr Neurol Neurosci Rep. 2005 Sep;5(5):397-404
references: 16131423
references: Curr Biol. 2007 Apr 3;17(7):592-8
references: 17346966
references: Commun Integr Biol. 2010 Sep;3(5):396-400
references: 21057624
references: Neurosci Lett. 2006 Dec 20;410(2):80-4
references: 17095157
references: J Neurochem. 2009 May;109(4):959-68
references: 19302196
references: Biochemistry. 2009 Nov 24;48(46):10963-75
references: 19824698
references: Science. 2002 Jun 14;296(5575):1991-5
references: 12065827
references: Anal Biochem. 2010 Sep 15;404(2):186-92
references: 20566370
references: ASN Neuro. 2009 Apr 14;1(1):
references: 19570025
references: Mol Neurodegener. 2008 Feb 08;3:3
references: 18257932
references: Neurodegener Dis. 2010;7(1-3):68-75
references: 20173330
references: Proc Natl Acad Sci U S A. 1975 May;72(5):1858-62
references: 1057175
references: Neuroscience. 2007 Jul 29;147(4):1047-58
references: 17611037
references: J Neurosci. 2010 Sep 29;30(39):13138-49
references: 20881132
references: Science. 2002 Feb 1;295(5556):865-8
references: 11823645
references: J Biol Chem. 2005 Jan 28;280(4):2873-8
references: 15556931
references: PLoS Genet. 2010 Apr 08;6(4):e1000902
references: 20386743
references: Nat Med. 2004 Jul;10 Suppl:S10-7
references: 15272267
references: Neurodegener Dis. 2008;5(3-4):182-5
references: 18322385
references: Neurobiol Dis. 2006 Aug;23(2):329-41
references: 16750377
references: Eur J Neurol. 2011 Apr;18(4):545-6
references: 21199179
references: Neuron. 2003 Sep 11;39(6):889-909
references: 12971891
references: J Biol Chem. 2009 Dec 25;284(52):36346-36356
references: 19826009
references: Exp Cell Res. 2008 Jun 10;314(10):2055-65
references: 18445495
references: J Biol Chem. 2009 Jun 12;284(24):16482-16491
references: 19251702
references: Biochem Biophys Res Commun. 2007 Jun 8;357(3):668-71
references: 17442267
references: Exp Cell Res. 2010 Feb 15;316(4):649-56
references: 19769964
references: J Neurosci. 2009 Nov 4;29(44):13971-80
references: 19890007
references: Biochemistry. 2010 Mar 9;49(9):2008-17
references: 20146535
references: Biochim Biophys Acta. 2010 Sep;1804(9):1780-4
references: 20493972
references: Pathol Biol (Paris). 2007 Mar;55(2):107-10
references: 16884863
references: Nature. 2000 Mar 23;404(6776):341, 343
references: 10746706
references: Brain. 2005 Dec;128(Pt 12):3000-11
references: 16251215
references: J Neurochem. 2009 Sep;110(5):1514-22
references: 19545277
references: Biochem Biophys Res Commun. 2007 Jun 29;358(2):534-9
references: 17498648
references: Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12517-22
references: 16894167
references: Biochem J. 2010 Sep 15;430(3):e5-6
references: 20795948
references: Eur J Neurosci. 2006 Feb;23(3):659-66
references: 16487147
references: EMBO J. 2008 Aug 20;27(16):2239-49
references: 18650931
references: Neuroscience. 2006;139(3):791-4
references: 16504409
references: Neuron. 2006 Oct 5;52(1):169-78
references: 17015234
references: Biochemistry. 2010 Jul 6;49(26):5511-23
references: 20515039
references: J Neurosci. 2009 Jan 28;29(4):1011-6
references: 19176810
references: Trends Neurosci. 2006 May;29(5):286-93
references: 16616379
references: Biochem J. 2007 Jul 15;405(2):307-17
references: 17447891
references: Biochim Biophys Acta. 1998 Jun 29;1376(1):27-55
references: 9666066
references: Nature. 2000 Mar 23;404(6776):394-8
references: 10746727