title: Emerging common molecular pathways for primary dystonia.
abstract: The dystonias are a group of hyperkinetic movement disorders whose principal cause is neuron dysfunction at 1 or more interconnected nodes of the motor system. The study of genes and proteins that cause familial dystonia provides critical information about the cellular pathways involved in this dysfunction, which disrupts the motor pathways at the systems level. In recent years study of the increasing number of DYT genes has implicated a number of cell functions that appear to be involved in the pathogenesis of dystonia. A review of the literature published in English-language publications available on PubMed relating to the genetics and cellular pathology of dystonia was performed. Numerous potential pathogenetic mechanisms have been identified. We describe those that fall into 3 emerging thematic groups: cell-cycle and transcriptional regulation in the nucleus, endoplasmic reticulum and nuclear envelope function, and control of synaptic function. © 2013 Movement Disorder Society.
authors.affiliation: Department of Neurology, University of Tennessee Health Science Center Memphis, Tennessee 38163, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Ledoux
authors.forename: William T
authors.initials: WT
authors.lastname: Dauer
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Warner
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D020821:Dystonic Disorders / Q000235:genetics* / Q000473:pathology; D004721:Endoplasmic Reticulum / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D039781:PubMed / Q000706:statistics & numerical data
chemical_list: D018832:Molecular Chaperones; D009687:Nuclear Proteins
keywords: DYT genes; cell cycle; endoplasmic reticulum; nuclear envelope; synaptic function
references.citation: Nat Genet. 1997 Sep;17(1):40-8
references.pmid: 9288096
references.citation: Proteomics Clin Appl. 2008 May;2(5):720-36
references.pmid: 21136869
references.citation: Proc Natl Acad Sci U S A. 2004 Jan 20;101(3):847-52
references.pmid: 14711988
references.citation: J Neurochem. 2007 Aug;102(3):783-8
references.pmid: 17550429
references.citation: Nat Neurosci. 2011 Mar;14(3):357-65
references.pmid: 21297628
references.citation: Curr Opin Cell Biol. 2011 Apr;23(2):176-83
references.pmid: 21075612
references.citation: Neuron. 2002 Feb 14;33(4):545-58
references.pmid: 11856529
references.citation: J Neurosci. 2011 May 18;31(20):7568-77
references.pmid: 21593342
references.citation: Neuron. 2005 Aug 4;47(3):339-52
references.pmid: 16055059
references.citation: Neurobiol Dis. 2011 May;42(2):136-47
references.pmid: 21134457
references.citation: Hum Genet. 2009 Sep;126(3):431-47
references.pmid: 19455355
references.citation: J Clin Psychiatry. 2004;65 Suppl 9:25-8
references.pmid: 15189109
references.citation: Nat Genet. 2013 Jan;45(1):88-92
references.pmid: 23222958
references.citation: Ann Neurol. 2010 Oct;68(4):554-9
references.pmid: 20976771
references.citation: Brain Res Dev Brain Res. 2005 Jun 9;157(1):19-26
references.pmid: 15939081
references.citation: Mol Cell. 2004 Mar 26;13(6):867-78
references.pmid: 15053879
references.citation: Nat Rev Mol Cell Biol. 2005 Jul;6(7):519-29
references.pmid: 16072036
references.citation: Neurosci Lett. 2003 May 29;343(1):5-8
references.pmid: 12749984
references.citation: J Cell Sci. 2008 Oct 15;121(Pt 20):3476-86
references.pmid: 18827015
references.citation: Cell Cycle. 2011 Oct 1;10(19):3239-48
references.pmid: 21921675
references.citation: J Neurol. 2006 Dec;253 Suppl 7:VII7-13
references.pmid: 17131231
references.citation: Parkinsonism Relat Disord. 2012 Jun;18(5):414-25
references.pmid: 22377579
references.citation: Proc Natl Acad Sci U S A. 2007 Apr 24;104(17):7271-6
references.pmid: 17428918
references.citation: Ann Neurol. 2010 Oct;68(4):549-53
references.pmid: 20865765
references.citation: Proc Natl Acad Sci U S A. 2004 May 18;101(20):7612-7
references.pmid: 15136718
references.citation: Hum Mol Genet. 2007 Feb 1;16(3):327-42
references.pmid: 17200151
references.citation: J Neurochem. 2010 Sep;114(6):1781-91
references.pmid: 20626557
references.citation: Ann Neurol. 1998 May;43(5):669-73
references.pmid: 9585364
references.citation: Nat Struct Mol Biol. 2010 Jan;17(1):117-23
references.pmid: 20010837
references.citation: Clin Neurophysiol. 2012 Jan;123(1):65-70
references.pmid: 22078259
references.citation: J Neurosci. 2001 Jun 15;21(12):4390-9
references.pmid: 11404425
references.citation: Curr Opin Cell Biol. 2011 Jun;23(3):338-45
references.pmid: 21292462
references.citation: Neuroscience. 2011 Aug 25;189:100-7
references.pmid: 21616129
references.citation: Development. 2002 Jan;129(2):373-85
references.pmid: 11807030
references.citation: Hum Mol Genet. 2013 Jun 15;22(12):2510-9
references.pmid: 23449625
references.citation: EMBO J. 2011 Jan 5;30(1):181-93
references.pmid: 21102408
references.citation: J Biol Chem. 2008 Mar 21;283(12):7568-79
references.pmid: 18167355
references.citation: Am J Hum Genet. 2007 Mar;80(3):393-406
references.pmid: 17273961
references.citation: J Cell Sci. 2005 Jan 1;118(Pt 1):101-12
references.pmid: 15585571
references.citation: Oncogene. 2003 Apr 24;22(16):2432-42
references.pmid: 12717420
references.citation: Biochem Soc Trans. 2011 Dec;39(6):1742-6
references.pmid: 22103518
references.citation: Mol Cell Biol. 2004 Jun;24(12):5332-9
references.pmid: 15169897
references.citation: Neuron. 2003 Jul 17;39(2):241-54
references.pmid: 12873382
references.citation: Neuron. 2005 Dec 22;48(6):923-32
references.pmid: 16364897
references.citation: J Neurosci. 2002 Jun 1;22(11):4274-85
references.pmid: 12040032
references.citation: Hum Mol Genet. 2010 Sep 15;19(18):3502-15
references.pmid: 20584926
references.citation: J Biol Chem. 2009 Feb 6;284(6):3672-81
references.pmid: 19001364
references.citation: Mol Cell Neurosci. 2010 Oct;45(2):151-62
references.pmid: 20600931
references.citation: Mol Cell Biol. 2006 Dec;26(24):9256-67
references.pmid: 17030624
references.citation: Mov Disord. 2005 Apr;20(4):432-40
references.pmid: 15593317
references.citation: Neurobiol Dis. 2010 Jun;38(3):434-45
references.pmid: 20227500
references.citation: Lancet Neurol. 2011 Dec;10(12):1074-85
references.pmid: 22030388
references.citation: Hum Mutat. 2011 Nov;32(11):1213-24
references.pmid: 21793105
references.citation: J Neurochem. 2010 Apr;113(1):228-35
references.pmid: 20132487
references.citation: Mov Disord. 2011 Apr;26(5):858-61
references.pmid: 21425335
references.citation: Neurobiol Dis. 2003 Feb;12(1):11-24
references.pmid: 12609485
references.citation: Hum Mol Genet. 2006 Apr 15;15(8):1355-64
references.pmid: 16537570
references.citation: Ann Neurol. 1999 Nov;46(5):761-9
references.pmid: 10553994
references.citation: J Neurosci. 2004 Mar 17;24(11):2593-601
references.pmid: 15028751
references.citation: Trends Cell Biol. 2006 Feb;16(2):67-9
references.pmid: 16406617
references.citation: J Med Invest. 2005 Nov;52 Suppl:272-9
references.pmid: 16366514
references.citation: Hum Mol Genet. 2004 Sep 15;13(18):2019-30
references.pmid: 15269177
references.citation: Synapse. 2012 May;66(5):453-64
references.pmid: 22213465
references.citation: Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):8839-40
references.pmid: 15187229
references.citation: Mov Disord. 2011 Sep;26(11):2136-7
references.pmid: 21638323
references.citation: Curr Opin Neurol. 1997 Apr;10(2):168-75
references.pmid: 9146999
references.citation: Hum Mol Genet. 2008 Sep 1;17(17):2712-22
references.pmid: 18552369
references.citation: J Cell Sci. 2010 Apr 1;123(Pt 7):1108-15
references.pmid: 20215406
references.citation: Ann Neurol. 2012 Apr;71(4):458-69
references.pmid: 22447717
references.citation: Neurobiol Dis. 2009 Apr;34(1):133-45
references.pmid: 19187797
references.citation: Brain Res Dev Brain Res. 2004 Aug 18;152(1):47-60
references.pmid: 15283994
references.citation: Neurobiol Dis. 2006 Apr;22(1):98-111
references.pmid: 16361107
references.citation: Nat Commun. 2011 Jul 12;2:393
references.pmid: 21750546
references.citation: Neurobiol Dis. 2013 Jun;54:362-71
references.pmid: 23336980
references.citation: Brain Res. 2006 Feb 16;1073-1074:139-45
references.pmid: 16458269
references.citation: Nucleic Acids Res. 2010 Jun;38(10):3466-76
references.pmid: 20144952
references.citation: Biochem Biophys Res Commun. 1999 Oct 22;264(2):457-64
references.pmid: 10529385
references.citation: Neurobiol Dis. 2006 Nov;24(2):318-25
references.pmid: 16934985
references.citation: J Neurosci. 1987 Mar;7(3):829-36
references.pmid: 3559714
references.citation: Hum Mol Genet. 2008 May 15;17(10):1436-45
references.pmid: 18258738
references.citation: FEBS Lett. 2007 Sep 4;581(22):4325-32
references.pmid: 17716668
references.citation: J Neurol Neurosurg Psychiatry. 2009 Aug;80(8):839-45
references.pmid: 19332422
references.citation: J Comp Neurol. 2005 Jan 31;482(1):50-73
references.pmid: 15612018
references.citation: Ann Neurol. 2013 Apr;73(4):546-53
references.pmid: 23424103
references.citation: Cancer Res. 2006 Nov 15;66(22):11021-9
references.pmid: 17108141
references.citation: Lancet Neurol. 2009 May;8(5):441-6
references.pmid: 19345147
references.citation: Lancet Neurol. 2008 Mar;7(3):207-15
references.pmid: 18243799
references.citation: Mov Disord. 2012 Jun;27(7):917
references.pmid: 22508326
references.citation: Proc Natl Acad Sci U S A. 2005 May 10;102(19):6907-12
references.pmid: 15863623
references.citation: Brain Res. 2004 Jun 25;1012(1-2):75-81
references.pmid: 15158163
references.citation: J Biomed Sci. 2003 Jul-Aug;10(4):406-17
references.pmid: 12824700
references.citation: Neurology. 2002 Aug 13;59(3):445-8
references.pmid: 12177384
references.citation: Exp Neurol. 2013 Mar;241:95-104
references.pmid: 23195594
references.citation: Development. 2001 Nov;128(22):4645-56
references.pmid: 11714689
references.citation: Hum Mol Genet. 2010 Mar 1;19(5):888-900
references.pmid: 20015956
references.citation: J Neurosci. 1997 Jan 15;17(2):843-50
references.pmid: 8987805
references.citation: Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15650-5
references.pmid: 15505207
references.citation: J Cell Sci. 2007 Jan 1;120(Pt 1):115-24
references.pmid: 17182902
references.citation: Blood. 2007 Jan 15;109(2):584-94
references.pmid: 17003378
references.citation: Neuroscience. 2008 Aug 13;155(2):439-53
references.pmid: 18538941
references.citation: Mov Disord. 2002 Nov;17(6):1271-7
references.pmid: 12465067
references.citation: Hum Mol Genet. 2005 Jan 1;14(1):125-33
references.pmid: 15548549
references.citation: Neurobiol Dis. 2007 May;26(2):396-407
references.pmid: 17374562
references.citation: J Neurosci. 2002 Jun 15;22(12):4805-13
references.pmid: 12077177
references.citation: Neurology. 2002 Jan 8;58(1):124-6
references.pmid: 11781417
references.citation: Lancet Neurol. 2011 Jan;10(1):54-62
references.pmid: 21112253
references.citation: Neuroscience. 2013 Feb 12;231:282-95
references.pmid: 23219941
references.citation: J Biol Chem. 2008 Feb 15;283(7):4352-63
references.pmid: 18073205
references.citation: Hum Mol Genet. 1995 Jul;4(7):1209-12
references.pmid: 8528210
references.citation: Synapse. 2012 Sep;66(9):807-22
references.pmid: 22588999
references.citation: Curr Opin Neurol. 1995 Oct;8(5):379-84
references.pmid: 8542044
references.citation: Nat Genet. 2009 Mar;41(3):286-8
references.pmid: 19182804
references.citation: Am J Hum Genet. 2012 Dec 7;91(6):1041-50
references.pmid: 23200863
references.citation: Eur J Neurol. 2010 Jul;17 Suppl 1:58-64
references.pmid: 20590810
references.citation: Exp Neurol. 2005 Dec;196(2):452-63
references.pmid: 16242683
references.citation: Lancet Neurol. 2009 May;8(5):447-52
references.pmid: 19345148
references.citation: Neurobiol Dis. 2012 Oct;48(1):66-78
references.pmid: 22659308
references.citation: Nature. 2005 Oct 20;437(7062):1173-8
references.pmid: 16189514
references.citation: Nat Genet. 1994 Nov;8(3):236-42
references.pmid: 7874165
references.citation: J Clin Invest. 2009 Jun;119(6):1595-603
references.pmid: 19478460
references.citation: Neurology. 2012 Feb 28;78(9):649-57
references.pmid: 22345219
references.citation: Neurobiol Dis. 2010 Sep;39(3):318-26
references.pmid: 20460154
references.citation: J Cell Biol. 2005 Mar 14;168(6):855-62
references.pmid: 15767459
references.citation: Nat Genet. 2001 Sep;29(1):66-9
references.pmid: 11528394
references.citation: Clin Cancer Res. 2006 May 1;12(9):2657-61
references.pmid: 16675556
references.citation: J Neurosci. 2007 Nov 14;27(46):12555-64
references.pmid: 18003834
references.citation: Exp Neurol. 2008 Apr;210(2):719-30
references.pmid: 18299128
references.citation: Neurology. 2009 Jun 16;72(24):2097-103
references.pmid: 19528516
references.citation: Neurology. 2000 Mar 14;54(5):1193-5
references.pmid: 10720299
references.citation: Neuropsychopharmacology. 2009 Jun;34(7):1710-20
references.pmid: 19158668
references.citation: Neurobiol Dis. 2011 May;42(2):162-70
references.pmid: 21168494