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Published in: neurogenetics 4/2015

Open Access 01-10-2015 | Review article

Splicing: is there an alternative contribution to Parkinson’s disease?

Authors: Valentina La Cognata, Velia D’Agata, Francesca Cavalcanti, Sebastiano Cavallaro

Published in: Neurogenetics | Issue 4/2015

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Abstract

Alternative splicing is a crucial mechanism of gene expression regulation that enormously increases the coding potential of our genome and represents an intermediate step between messenger RNA (mRNA) transcription and protein posttranslational modifications. Alternative splicing occupies a central position in the development and functions of the nervous system. Therefore, its deregulation frequently leads to several neurological human disorders. In the present review, we provide an updated overview on the impact of alternative splicing in Parkinson’s disease (PD), the second most common neurodegenerative disorder worldwide. We will describe the alternative splicing of major PD-linked genes by collecting the current evidences about this intricate and not carefully explored aspect. Assessing the role of this mechanism on PD pathobiology may represent a central step toward an improved understanding of this complex disease.
Literature
5.
go back to reference Pan Q, Shai O, Lee LJ, Frey BJ, Blencowe BJ (2008) Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat Genet 40(12):1413–1415. doi:10.1038/ng.259 PubMedCrossRef Pan Q, Shai O, Lee LJ, Frey BJ, Blencowe BJ (2008) Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat Genet 40(12):1413–1415. doi:10.​1038/​ng.​259 PubMedCrossRef
6.
18.
go back to reference Nalls MA, Pankratz N, Lill CM, Do CB, Hernandez DG, Saad M, DeStefano AL, Kara E, Bras J, Sharma M, Schulte C, Keller MF, Arepalli S, Letson C, Edsall C, Stefansson H, Liu X, Pliner H, Lee JH, Cheng R, International Parkinson’s Disease Genomics C, Parkinson’s Study Group Parkinson’s Research: The Organized GI, andMe, GenePd, NeuroGenetics Research C, Hussman Institute of Human G, Ashkenazi Jewish Dataset I, Cohorts for H, Aging Research in Genetic E, North American Brain Expression C, United Kingdom Brain Expression C, Greek Parkinson’s Disease C, Alzheimer Genetic Analysis G, Ikram MA, Ioannidis JP, Hadjigeorgiou GM, Bis JC, Martinez M, Perlmutter JS, Goate A, Marder K, Fiske B, Sutherland M, Xiromerisiou G, Myers RH, Clark LN, Stefansson K, Hardy JA, Heutink P, Chen H, Wood NW, Houlden H, Payami H, Brice A, Scott WK, Gasser T, Bertram L, Eriksson N, Foroud T, Singleton AB (2014) Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease. Nat Genet 46(9):989–993. doi:10.1038/ng.3043 PubMedCentralPubMedCrossRef Nalls MA, Pankratz N, Lill CM, Do CB, Hernandez DG, Saad M, DeStefano AL, Kara E, Bras J, Sharma M, Schulte C, Keller MF, Arepalli S, Letson C, Edsall C, Stefansson H, Liu X, Pliner H, Lee JH, Cheng R, International Parkinson’s Disease Genomics C, Parkinson’s Study Group Parkinson’s Research: The Organized GI, andMe, GenePd, NeuroGenetics Research C, Hussman Institute of Human G, Ashkenazi Jewish Dataset I, Cohorts for H, Aging Research in Genetic E, North American Brain Expression C, United Kingdom Brain Expression C, Greek Parkinson’s Disease C, Alzheimer Genetic Analysis G, Ikram MA, Ioannidis JP, Hadjigeorgiou GM, Bis JC, Martinez M, Perlmutter JS, Goate A, Marder K, Fiske B, Sutherland M, Xiromerisiou G, Myers RH, Clark LN, Stefansson K, Hardy JA, Heutink P, Chen H, Wood NW, Houlden H, Payami H, Brice A, Scott WK, Gasser T, Bertram L, Eriksson N, Foroud T, Singleton AB (2014) Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease. Nat Genet 46(9):989–993. doi:10.​1038/​ng.​3043 PubMedCentralPubMedCrossRef
22.
go back to reference Nuytemans K, Meeus B, Crosiers D, Brouwers N, Goossens D, Engelborghs S, Pals P, Pickut B, Van den Broeck M, Corsmit E, Cras P, De Deyn PP, Del-Favero J, Van Broeckhoven C, Theuns J (2009) Relative contribution of simple mutations vs. copy number variations in five Parkinson disease genes in the Belgian population. Hum Mutat 30(7):1054–1061. doi:10.1002/humu.21007 PubMedCrossRef Nuytemans K, Meeus B, Crosiers D, Brouwers N, Goossens D, Engelborghs S, Pals P, Pickut B, Van den Broeck M, Corsmit E, Cras P, De Deyn PP, Del-Favero J, Van Broeckhoven C, Theuns J (2009) Relative contribution of simple mutations vs. copy number variations in five Parkinson disease genes in the Belgian population. Hum Mutat 30(7):1054–1061. doi:10.​1002/​humu.​21007 PubMedCrossRef
23.
24.
25.
go back to reference McLean JR, Hallett PJ, Cooper O, Stanley M, Isacson O (2012) Transcript expression levels of full-length alpha-synuclein and its three alternatively spliced variants in Parkinson’s disease brain regions and in a transgenic mouse model of alpha-synuclein overexpression. Mol Cell Neurosci 49(2):230–239. doi:10.1016/j.mcn.2011.11.006 PubMedCentralPubMedCrossRef McLean JR, Hallett PJ, Cooper O, Stanley M, Isacson O (2012) Transcript expression levels of full-length alpha-synuclein and its three alternatively spliced variants in Parkinson’s disease brain regions and in a transgenic mouse model of alpha-synuclein overexpression. Mol Cell Neurosci 49(2):230–239. doi:10.​1016/​j.​mcn.​2011.​11.​006 PubMedCentralPubMedCrossRef
26.
go back to reference Cardo LF, Coto E, de Mena L, Ribacoba R, Mata IF, Menendez M, Moris G, Alvarez V (2014) Alpha-synuclein transcript isoforms in three different brain regions from Parkinson’s disease and healthy subjects in relation to the SNCA rs356165/rs11931074 polymorphisms. Neurosci Lett 562:45–49. doi:10.1016/j.neulet.2014.01.009 PubMedCrossRef Cardo LF, Coto E, de Mena L, Ribacoba R, Mata IF, Menendez M, Moris G, Alvarez V (2014) Alpha-synuclein transcript isoforms in three different brain regions from Parkinson’s disease and healthy subjects in relation to the SNCA rs356165/rs11931074 polymorphisms. Neurosci Lett 562:45–49. doi:10.​1016/​j.​neulet.​2014.​01.​009 PubMedCrossRef
36.
go back to reference Johnson J, Paisan-Ruiz C, Lopez G, Crews C, Britton A, Malkani R, Evans EW, McInerney-Leo A, Jain S, Nussbaum RL, Foote KD, Mandel RJ, Crawley A, Reimsnider S, Fernandez HH, Okun MS, Gwinn-Hardy K, Singleton AB (2007) Comprehensive screening of a North American Parkinson’s disease cohort for LRRK2 mutation. Neurodegener Dis 4(5):386–391. doi:10.1159/000105160 PubMedCrossRef Johnson J, Paisan-Ruiz C, Lopez G, Crews C, Britton A, Malkani R, Evans EW, McInerney-Leo A, Jain S, Nussbaum RL, Foote KD, Mandel RJ, Crawley A, Reimsnider S, Fernandez HH, Okun MS, Gwinn-Hardy K, Singleton AB (2007) Comprehensive screening of a North American Parkinson’s disease cohort for LRRK2 mutation. Neurodegener Dis 4(5):386–391. doi:10.​1159/​000105160 PubMedCrossRef
37.
39.
go back to reference Shojaee S, Sina F, Farboodi N, Fazlali Z, Ghazavi F, Ghorashi SA, Parsa K, Sadeghi H, Shahidi GA, Ronaghi M, Elahi E (2009) A clinic-based screening of mutations in exons 31, 34, 35, 41, and 48 of LRRK2 in Iranian Parkinson’s disease patients. Mov Disord 24(7):1023–1027. doi:10.1002/mds.22503 PubMedCrossRef Shojaee S, Sina F, Farboodi N, Fazlali Z, Ghazavi F, Ghorashi SA, Parsa K, Sadeghi H, Shahidi GA, Ronaghi M, Elahi E (2009) A clinic-based screening of mutations in exons 31, 34, 35, 41, and 48 of LRRK2 in Iranian Parkinson’s disease patients. Mov Disord 24(7):1023–1027. doi:10.​1002/​mds.​22503 PubMedCrossRef
40.
go back to reference Di Fonzo A, Tassorelli C, De Mari M, Chien HF, Ferreira J, Rohe CF, Riboldazzi G, Antonini A, Albani G, Mauro A, Marconi R, Abbruzzese G, Lopiano L, Fincati E, Guidi M, Marini P, Stocchi F, Onofrj M, Toni V, Tinazzi M, Fabbrini G, Lamberti P, Vanacore N, Meco G, Leitner P, Uitti RJ, Wszolek ZK, Gasser T, Simons EJ, Breedveld GJ, Goldwurm S, Pezzoli G, Sampaio C, Barbosa E, Martignoni E, Oostra BA, Bonifati V, Italian Parkinson’s Genetics N (2006) Comprehensive analysis of the LRRK2 gene in sixty families with Parkinson’s disease. Eur J Hum Genet 14(3):322–331. doi:10.1038/sj.ejhg.5201539 PubMedCrossRef Di Fonzo A, Tassorelli C, De Mari M, Chien HF, Ferreira J, Rohe CF, Riboldazzi G, Antonini A, Albani G, Mauro A, Marconi R, Abbruzzese G, Lopiano L, Fincati E, Guidi M, Marini P, Stocchi F, Onofrj M, Toni V, Tinazzi M, Fabbrini G, Lamberti P, Vanacore N, Meco G, Leitner P, Uitti RJ, Wszolek ZK, Gasser T, Simons EJ, Breedveld GJ, Goldwurm S, Pezzoli G, Sampaio C, Barbosa E, Martignoni E, Oostra BA, Bonifati V, Italian Parkinson’s Genetics N (2006) Comprehensive analysis of the LRRK2 gene in sixty families with Parkinson’s disease. Eur J Hum Genet 14(3):322–331. doi:10.​1038/​sj.​ejhg.​5201539 PubMedCrossRef
41.
go back to reference Grimes DA, Racacho L, Han F, Panisset M, Bulman DE (2007) LRRK2 screening in a Canadian Parkinson’s disease cohort. Can J Neurol Sci 34(3):336–338PubMedCrossRef Grimes DA, Racacho L, Han F, Panisset M, Bulman DE (2007) LRRK2 screening in a Canadian Parkinson’s disease cohort. Can J Neurol Sci 34(3):336–338PubMedCrossRef
42.
go back to reference Paisan-Ruiz C, Nath P, Washecka N, Gibbs JR, Singleton AB (2008) Comprehensive analysis of LRRK2 in publicly available Parkinson’s disease cases and neurologically normal controls. Hum Mutat 29(4):485–490. doi:10.1002/humu.20668 PubMedCrossRef Paisan-Ruiz C, Nath P, Washecka N, Gibbs JR, Singleton AB (2008) Comprehensive analysis of LRRK2 in publicly available Parkinson’s disease cases and neurologically normal controls. Hum Mutat 29(4):485–490. doi:10.​1002/​humu.​20668 PubMedCrossRef
43.
go back to reference Lesage S, Condroyer C, Lannuzel A, Lohmann E, Troiano A, Tison F, Damier P, Thobois S, Ouvrard-Hernandez AM, Rivaud-Pechoux S, Brefel-Courbon C, Destee A, Tranchant C, Romana M, Leclere L, Durr A, Brice A, French Parkinson’s Disease Genetics Study G (2009) Molecular analyses of the LRRK2 gene in European and North African autosomal dominant Parkinson’s disease. J Med Genet 46(7):458–464. doi:10.1136/jmg.2008.062612 PubMedCrossRef Lesage S, Condroyer C, Lannuzel A, Lohmann E, Troiano A, Tison F, Damier P, Thobois S, Ouvrard-Hernandez AM, Rivaud-Pechoux S, Brefel-Courbon C, Destee A, Tranchant C, Romana M, Leclere L, Durr A, Brice A, French Parkinson’s Disease Genetics Study G (2009) Molecular analyses of the LRRK2 gene in European and North African autosomal dominant Parkinson’s disease. J Med Genet 46(7):458–464. doi:10.​1136/​jmg.​2008.​062612 PubMedCrossRef
44.
go back to reference Trabzuni D, Ryten M, Emmett W, Ramasamy A, Lackner KJ, Zeller T, Walker R, Smith C, Lewis PA, Mamais A, de Silva R, Vandrovcova J, International Parkinson Disease Genomics C, Hernandez D, Nalls MA, Sharma M, Garnier S, Lesage S, Simon-Sanchez J, Gasser T, Heutink P, Brice A, Singleton A, Cai H, Schadt E, Wood NW, Bandopadhyay R, Weale ME, Hardy J, Plagnol V (2013) Fine-mapping, gene expression and splicing analysis of the disease associated LRRK2 locus. PLoS ONE 8(8):e70724. doi:10.1371/journal.pone.0070724 PubMedCentralPubMedCrossRef Trabzuni D, Ryten M, Emmett W, Ramasamy A, Lackner KJ, Zeller T, Walker R, Smith C, Lewis PA, Mamais A, de Silva R, Vandrovcova J, International Parkinson Disease Genomics C, Hernandez D, Nalls MA, Sharma M, Garnier S, Lesage S, Simon-Sanchez J, Gasser T, Heutink P, Brice A, Singleton A, Cai H, Schadt E, Wood NW, Bandopadhyay R, Weale ME, Hardy J, Plagnol V (2013) Fine-mapping, gene expression and splicing analysis of the disease associated LRRK2 locus. PLoS ONE 8(8):e70724. doi:10.​1371/​journal.​pone.​0070724 PubMedCentralPubMedCrossRef
47.
go back to reference Vilarino-Guell C, Wider C, Ross OA, Dachsel JC, Kachergus JM, Lincoln SJ, Soto-Ortolaza AI, Cobb SA, Wilhoite GJ, Bacon JA, Behrouz B, Melrose HL, Hentati E, Puschmann A, Evans DM, Conibear E, Wasserman WW, Aasly JO, Burkhard PR, Djaldetti R, Ghika J, Hentati F, Krygowska-Wajs A, Lynch T, Melamed E, Rajput A, Rajput AH, Solida A, Wu RM, Uitti RJ, Wszolek ZK, Vingerhoets F, Farrer MJ (2011) VPS35 mutations in Parkinson disease. Am J Hum Genet 89(1):162–167. doi:10.1016/j.ajhg.2011.06.001 PubMedCentralPubMedCrossRef Vilarino-Guell C, Wider C, Ross OA, Dachsel JC, Kachergus JM, Lincoln SJ, Soto-Ortolaza AI, Cobb SA, Wilhoite GJ, Bacon JA, Behrouz B, Melrose HL, Hentati E, Puschmann A, Evans DM, Conibear E, Wasserman WW, Aasly JO, Burkhard PR, Djaldetti R, Ghika J, Hentati F, Krygowska-Wajs A, Lynch T, Melamed E, Rajput A, Rajput AH, Solida A, Wu RM, Uitti RJ, Wszolek ZK, Vingerhoets F, Farrer MJ (2011) VPS35 mutations in Parkinson disease. Am J Hum Genet 89(1):162–167. doi:10.​1016/​j.​ajhg.​2011.​06.​001 PubMedCentralPubMedCrossRef
48.
go back to reference Zimprich A, Benet-Pages A, Struhal W, Graf E, Eck SH, Offman MN, Haubenberger D, Spielberger S, Schulte EC, Lichtner P, Rossle SC, Klopp N, Wolf E, Seppi K, Pirker W, Presslauer S, Mollenhauer B, Katzenschlager R, Foki T, Hotzy C, Reinthaler E, Harutyunyan A, Kralovics R, Peters A, Zimprich F, Brucke T, Poewe W, Auff E, Trenkwalder C, Rost B, Ransmayr G, Winkelmann J, Meitinger T, Strom TM (2011) A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson disease. Am J Hum Genet 89(1):168–175. doi:10.1016/j.ajhg.2011.06.008 PubMedCentralPubMedCrossRef Zimprich A, Benet-Pages A, Struhal W, Graf E, Eck SH, Offman MN, Haubenberger D, Spielberger S, Schulte EC, Lichtner P, Rossle SC, Klopp N, Wolf E, Seppi K, Pirker W, Presslauer S, Mollenhauer B, Katzenschlager R, Foki T, Hotzy C, Reinthaler E, Harutyunyan A, Kralovics R, Peters A, Zimprich F, Brucke T, Poewe W, Auff E, Trenkwalder C, Rost B, Ransmayr G, Winkelmann J, Meitinger T, Strom TM (2011) A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson disease. Am J Hum Genet 89(1):168–175. doi:10.​1016/​j.​ajhg.​2011.​06.​008 PubMedCentralPubMedCrossRef
49.
go back to reference Verstraeten A, Wauters E, Crosiers D, Meeus B, Corsmit E, Elinck E, Mattheijssens M, Peeters K, Cras P, Pickut B, Vandenberghe R, Engelborghs S, De Deyn PP, Van Broeckhoven C (1844) Theuns J (2012) Contribution of VPS35 genetic variability to LBD in the Flanders–Belgian population. Neurobiol Aging 33(8):e1811–e1843. doi:10.1016/j.neurobiolaging.2012.01.006 Verstraeten A, Wauters E, Crosiers D, Meeus B, Corsmit E, Elinck E, Mattheijssens M, Peeters K, Cras P, Pickut B, Vandenberghe R, Engelborghs S, De Deyn PP, Van Broeckhoven C (1844) Theuns J (2012) Contribution of VPS35 genetic variability to LBD in the Flanders–Belgian population. Neurobiol Aging 33(8):e1811–e1843. doi:10.​1016/​j.​neurobiolaging.​2012.​01.​006
51.
go back to reference Lucking CB, Durr A, Bonifati V, Vaughan J, De Michele G, Gasser T, Harhangi BS, Meco G, Denefle P, Wood NW, Agid Y, Brice A, French Parkinson’s Disease Genetics Study G, European Consortium on Genetic Susceptibility in Parkinson’s D (2000) Association between early-onset Parkinson’s disease and mutations in the parkin gene. N Engl J Med 342(21):1560–1567. doi:10.1056/NEJM200005253422103 PubMedCrossRef Lucking CB, Durr A, Bonifati V, Vaughan J, De Michele G, Gasser T, Harhangi BS, Meco G, Denefle P, Wood NW, Agid Y, Brice A, French Parkinson’s Disease Genetics Study G, European Consortium on Genetic Susceptibility in Parkinson’s D (2000) Association between early-onset Parkinson’s disease and mutations in the parkin gene. N Engl J Med 342(21):1560–1567. doi:10.​1056/​NEJM200005253422​103 PubMedCrossRef
52.
go back to reference Oliveira SA, Scott WK, Martin ER, Nance MA, Watts RL, Hubble JP, Koller WC, Pahwa R, Stern MB, Hiner BC, Ondo WG, Allen FH Jr, Scott BL, Goetz CG, Small GW, Mastaglia F, Stajich JM, Zhang F, Booze MW, Winn MP, Middleton LT, Haines JL, Pericak-Vance MA, Vance JM (2003) Parkin mutations and susceptibility alleles in late-onset Parkinson’s disease. Ann Neurol 53(5):624–629. doi:10.1002/ana.10524 PubMedCrossRef Oliveira SA, Scott WK, Martin ER, Nance MA, Watts RL, Hubble JP, Koller WC, Pahwa R, Stern MB, Hiner BC, Ondo WG, Allen FH Jr, Scott BL, Goetz CG, Small GW, Mastaglia F, Stajich JM, Zhang F, Booze MW, Winn MP, Middleton LT, Haines JL, Pericak-Vance MA, Vance JM (2003) Parkin mutations and susceptibility alleles in late-onset Parkinson’s disease. Ann Neurol 53(5):624–629. doi:10.​1002/​ana.​10524 PubMedCrossRef
53.
go back to reference Illarioshkin SN, Periquet M, Rawal N, Lucking CB, Zagorovskaya TB, Slominsky PA, Miloserdova OV, Markova ED, Limborska SA, Ivanova-Smolenskaya IA, Brice A (2003) Mutation analysis of the parkin gene in Russian families with autosomal recessive juvenile parkinsonism. Mov Disord 18(8):914–919. doi:10.1002/mds.10467 PubMedCrossRef Illarioshkin SN, Periquet M, Rawal N, Lucking CB, Zagorovskaya TB, Slominsky PA, Miloserdova OV, Markova ED, Limborska SA, Ivanova-Smolenskaya IA, Brice A (2003) Mutation analysis of the parkin gene in Russian families with autosomal recessive juvenile parkinsonism. Mov Disord 18(8):914–919. doi:10.​1002/​mds.​10467 PubMedCrossRef
54.
go back to reference Pigullo S, De Luca A, Barone P, Marchese R, Bellone E, Colosimo A, Scaglione C, Martinelli P, Di Maria E, Pizzuti A, Abbruzzese G, Dallapiccola B, Ajmar F, Mandich P (2004) Mutational analysis of parkin gene by denaturing high-performance liquid chromatography (DHPLC) in essential tremor. Parkinsonism Relat Disord 10(6):357–362. doi:10.1016/j.parkreldis.2004.04.012 PubMedCrossRef Pigullo S, De Luca A, Barone P, Marchese R, Bellone E, Colosimo A, Scaglione C, Martinelli P, Di Maria E, Pizzuti A, Abbruzzese G, Dallapiccola B, Ajmar F, Mandich P (2004) Mutational analysis of parkin gene by denaturing high-performance liquid chromatography (DHPLC) in essential tremor. Parkinsonism Relat Disord 10(6):357–362. doi:10.​1016/​j.​parkreldis.​2004.​04.​012 PubMedCrossRef
55.
go back to reference Scherfler C, Khan NL, Pavese N, Eunson L, Graham E, Lees AJ, Quinn NP, Wood NW, Brooks DJ, Piccini PP (2004) Striatal and cortical pre- and postsynaptic dopaminergic dysfunction in sporadic parkin-linked parkinsonism. Brain 127(Pt 6):1332–1342. doi:10.1093/brain/awh150 PubMedCrossRef Scherfler C, Khan NL, Pavese N, Eunson L, Graham E, Lees AJ, Quinn NP, Wood NW, Brooks DJ, Piccini PP (2004) Striatal and cortical pre- and postsynaptic dopaminergic dysfunction in sporadic parkin-linked parkinsonism. Brain 127(Pt 6):1332–1342. doi:10.​1093/​brain/​awh150 PubMedCrossRef
56.
go back to reference Bertoli-Avella AM, Giroud-Benitez JL, Akyol A, Barbosa E, Schaap O, van der Linde HC, Martignoni E, Lopiano L, Lamberti P, Fincati E, Antonini A, Stocchi F, Montagna P, Squitieri F, Marini P, Abbruzzese G, Fabbrini G, Marconi R, Dalla Libera A, Trianni G, Guidi M, De Gaetano A, Boff Maegawa G, De Leo A, Gallai V, de Rosa G, Vanacore N, Meco G, van Duijn CM, Oostra BA, Heutink P, Bonifati V, Italian Parkinson Genetics N (2005) Novel parkin mutations detected in patients with early-onset Parkinson’s disease. Mov Disord 20(4):424–431. doi:10.1002/mds.20343 PubMedCrossRef Bertoli-Avella AM, Giroud-Benitez JL, Akyol A, Barbosa E, Schaap O, van der Linde HC, Martignoni E, Lopiano L, Lamberti P, Fincati E, Antonini A, Stocchi F, Montagna P, Squitieri F, Marini P, Abbruzzese G, Fabbrini G, Marconi R, Dalla Libera A, Trianni G, Guidi M, De Gaetano A, Boff Maegawa G, De Leo A, Gallai V, de Rosa G, Vanacore N, Meco G, van Duijn CM, Oostra BA, Heutink P, Bonifati V, Italian Parkinson Genetics N (2005) Novel parkin mutations detected in patients with early-onset Parkinson’s disease. Mov Disord 20(4):424–431. doi:10.​1002/​mds.​20343 PubMedCrossRef
60.
go back to reference Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392(6676):605–608PubMedCrossRef Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392(6676):605–608PubMedCrossRef
61.
go back to reference Matsumine H, Saito M, Shimoda-Matsubayashi S, Tanaka H, Ishikawa A, Nakagawa-Hattori Y, Yokochi M, Kobayashi T, Igarashi S, Takano H, Sanpei K, Koike R, Mori H, Kondo T, Mizutani Y, Schaffer AA, Yamamura Y, Nakamura S, Kuzuhara S, Tsuji S, Mizuno Y (1997) Localization of a gene for an autosomal recessive form of juvenile parkinsonism to chromosome 6q25.2–27. Am J Hum Genet 60(3):588–596PubMedCentralPubMed Matsumine H, Saito M, Shimoda-Matsubayashi S, Tanaka H, Ishikawa A, Nakagawa-Hattori Y, Yokochi M, Kobayashi T, Igarashi S, Takano H, Sanpei K, Koike R, Mori H, Kondo T, Mizutani Y, Schaffer AA, Yamamura Y, Nakamura S, Kuzuhara S, Tsuji S, Mizuno Y (1997) Localization of a gene for an autosomal recessive form of juvenile parkinsonism to chromosome 6q25.2–27. Am J Hum Genet 60(3):588–596PubMedCentralPubMed
63.
go back to reference Ikeuchi K, Marusawa H, Fujiwara M, Matsumoto Y, Endo Y, Watanabe T, Iwai A, Sakai Y, Takahashi R, Chiba T (2009) Attenuation of proteolysis-mediated cyclin E regulation by alternatively spliced parkin in human colorectal cancers. Int J Cancer 125(9):2029–2035. doi:10.1002/ijc.24565 PubMedCrossRef Ikeuchi K, Marusawa H, Fujiwara M, Matsumoto Y, Endo Y, Watanabe T, Iwai A, Sakai Y, Takahashi R, Chiba T (2009) Attenuation of proteolysis-mediated cyclin E regulation by alternatively spliced parkin in human colorectal cancers. Int J Cancer 125(9):2029–2035. doi:10.​1002/​ijc.​24565 PubMedCrossRef
64.
go back to reference Kitada T, Asakawa S, Minoshima S, Mizuno Y, Shimizu N (2000) Molecular cloning, gene expression, and identification of a splicing variant of the mouse parkin gene. Mamm Genome 11(6):417–421PubMedCrossRef Kitada T, Asakawa S, Minoshima S, Mizuno Y, Shimizu N (2000) Molecular cloning, gene expression, and identification of a splicing variant of the mouse parkin gene. Mamm Genome 11(6):417–421PubMedCrossRef
66.
go back to reference Tan EK, Shen H, Tan JM, Lim KL, Fook-Chong S, Hu WP, Paterson MC, Chandran VR, Yew K, Tan C, Yuen Y, Pavanni R, Wong MC, Puvan K, Zhao Y (2005) Differential expression of splice variant and wild-type parkin in sporadic Parkinson’s disease. Neurogenetics 6(4):179–184. doi:10.1007/s10048-005-0001-5 PubMedCrossRef Tan EK, Shen H, Tan JM, Lim KL, Fook-Chong S, Hu WP, Paterson MC, Chandran VR, Yew K, Tan C, Yuen Y, Pavanni R, Wong MC, Puvan K, Zhao Y (2005) Differential expression of splice variant and wild-type parkin in sporadic Parkinson’s disease. Neurogenetics 6(4):179–184. doi:10.​1007/​s10048-005-0001-5 PubMedCrossRef
67.
go back to reference Dagata V, Cavallaro S (2004) Parkin transcript variants in rat and human brain. Neurochem Res 29(9):1715–1724PubMedCrossRef Dagata V, Cavallaro S (2004) Parkin transcript variants in rat and human brain. Neurochem Res 29(9):1715–1724PubMedCrossRef
68.
go back to reference Sunada Y, Saito F, Matsumura K, Shimizu T (1998) Differential expression of the parkin gene in the human brain and peripheral leukocytes. Neurosci Lett 254(3):180–182PubMedCrossRef Sunada Y, Saito F, Matsumura K, Shimizu T (1998) Differential expression of the parkin gene in the human brain and peripheral leukocytes. Neurosci Lett 254(3):180–182PubMedCrossRef
69.
go back to reference Solano SM, Miller DW, Augood SJ, Young AB, Penney JB Jr (2000) Expression of alpha-synuclein, parkin, and ubiquitin carboxy-terminal hydrolase L1 mRNA in human brain: genes associated with familial Parkinson’s disease. Ann Neurol 47(2):201–210PubMedCrossRef Solano SM, Miller DW, Augood SJ, Young AB, Penney JB Jr (2000) Expression of alpha-synuclein, parkin, and ubiquitin carboxy-terminal hydrolase L1 mRNA in human brain: genes associated with familial Parkinson’s disease. Ann Neurol 47(2):201–210PubMedCrossRef
71.
go back to reference Pawlyk AC, Giasson BI, Sampathu DM, Perez FA, Lim KL, Dawson VL, Dawson TM, Palmiter RD, Trojanowski JQ, Lee VM (2003) Novel monoclonal antibodies demonstrate biochemical variation of brain parkin with age. J Biol Chem 278(48):48120–48128. doi:10.1074/jbc.M306889200 PubMedCrossRef Pawlyk AC, Giasson BI, Sampathu DM, Perez FA, Lim KL, Dawson VL, Dawson TM, Palmiter RD, Trojanowski JQ, Lee VM (2003) Novel monoclonal antibodies demonstrate biochemical variation of brain parkin with age. J Biol Chem 278(48):48120–48128. doi:10.​1074/​jbc.​M306889200 PubMedCrossRef
72.
go back to reference Horowitz JM, Myers J, Stachowiak MK, Torres G (1999) Identification and distribution of Parkin in rat brain. Neuroreport 10(16):3393–3397PubMedCrossRef Horowitz JM, Myers J, Stachowiak MK, Torres G (1999) Identification and distribution of Parkin in rat brain. Neuroreport 10(16):3393–3397PubMedCrossRef
73.
go back to reference Stichel CC, Augustin M, Kuhn K, Zhu XR, Engels P, Ullmer C, Lubbert H (2000) Parkin expression in the adult mouse brain. Eur J Neurosci 12(12):4181–4194PubMed Stichel CC, Augustin M, Kuhn K, Zhu XR, Engels P, Ullmer C, Lubbert H (2000) Parkin expression in the adult mouse brain. Eur J Neurosci 12(12):4181–4194PubMed
74.
go back to reference Gu WJ, Abbas N, Lagunes MZ, Parent A, Pradier L, Bohme GA, Agid Y, Hirsch EC, Raisman-Vozari R, Brice A (2000) Cloning of rat parkin cDNA and distribution of parkin in rat brain. J Neurochem 74(4):1773–1776PubMedCrossRef Gu WJ, Abbas N, Lagunes MZ, Parent A, Pradier L, Bohme GA, Agid Y, Hirsch EC, Raisman-Vozari R, Brice A (2000) Cloning of rat parkin cDNA and distribution of parkin in rat brain. J Neurochem 74(4):1773–1776PubMedCrossRef
75.
go back to reference Huynh DP, Dy M, Nguyen D, Kiehl TR, Pulst SM (2001) Differential expression and tissue distribution of parkin isoforms during mouse development. Brain Res Dev Brain Res 130(2):173–181PubMedCrossRef Huynh DP, Dy M, Nguyen D, Kiehl TR, Pulst SM (2001) Differential expression and tissue distribution of parkin isoforms during mouse development. Brain Res Dev Brain Res 130(2):173–181PubMedCrossRef
76.
go back to reference D’Agata V, Grimaldi M, Pascale A, Cavallaro S (2000) Regional and cellular expression of the parkin gene in the rat cerebral cortex. Eur J Neurosci 12(10):3583–3588PubMedCrossRef D’Agata V, Grimaldi M, Pascale A, Cavallaro S (2000) Regional and cellular expression of the parkin gene in the rat cerebral cortex. Eur J Neurosci 12(10):3583–3588PubMedCrossRef
79.
go back to reference Marongiu R, Brancati F, Antonini A, Ialongo T, Ceccarini C, Scarciolla O, Capalbo A, Benti R, Pezzoli G, Dallapiccola B, Goldwurm S, Valente EM (2007) Whole gene deletion and splicing mutations expand the PINK1 genotypic spectrum. Hum Mutat 28(1):98. doi:10.1002/humu.9472 PubMedCrossRef Marongiu R, Brancati F, Antonini A, Ialongo T, Ceccarini C, Scarciolla O, Capalbo A, Benti R, Pezzoli G, Dallapiccola B, Goldwurm S, Valente EM (2007) Whole gene deletion and splicing mutations expand the PINK1 genotypic spectrum. Hum Mutat 28(1):98. doi:10.​1002/​humu.​9472 PubMedCrossRef
80.
go back to reference Samaranch L, Lorenzo-Betancor O, Arbelo JM, Ferrer I, Lorenzo E, Irigoyen J, Pastor MA, Marrero C, Isla C, Herrera-Henriquez J, Pastor P (2010) PINK1-linked parkinsonism is associated with Lewy body pathology. Brain 133(Pt 4):1128–1142. doi:10.1093/brain/awq051 PubMedCrossRef Samaranch L, Lorenzo-Betancor O, Arbelo JM, Ferrer I, Lorenzo E, Irigoyen J, Pastor MA, Marrero C, Isla C, Herrera-Henriquez J, Pastor P (2010) PINK1-linked parkinsonism is associated with Lewy body pathology. Brain 133(Pt 4):1128–1142. doi:10.​1093/​brain/​awq051 PubMedCrossRef
81.
go back to reference Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio AR, Healy DG, Albanese A, Nussbaum R, Gonzalez-Maldonado R, Deller T, Salvi S, Cortelli P, Gilks WP, Latchman DS, Harvey RJ, Dallapiccola B, Auburger G, Wood NW (2004) Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science 304(5674):1158–1160. doi:10.1126/science.1096284 PubMedCrossRef Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio AR, Healy DG, Albanese A, Nussbaum R, Gonzalez-Maldonado R, Deller T, Salvi S, Cortelli P, Gilks WP, Latchman DS, Harvey RJ, Dallapiccola B, Auburger G, Wood NW (2004) Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science 304(5674):1158–1160. doi:10.​1126/​science.​1096284 PubMedCrossRef
82.
go back to reference Silvestri L, Caputo V, Bellacchio E, Atorino L, Dallapiccola B, Valente EM, Casari G (2005) Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism. Hum Mol Genet 14(22):3477–3492. doi:10.1093/hmg/ddi377 PubMedCrossRef Silvestri L, Caputo V, Bellacchio E, Atorino L, Dallapiccola B, Valente EM, Casari G (2005) Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism. Hum Mol Genet 14(22):3477–3492. doi:10.​1093/​hmg/​ddi377 PubMedCrossRef
83.
go back to reference Beilina A, Van Der Brug M, Ahmad R, Kesavapany S, Miller DW, Petsko GA, Cookson MR (2005) Mutations in PTEN-induced putative kinase 1 associated with recessive parkinsonism have differential effects on protein stability. Proc Natl Acad Sci U S A 102(16):5703–5708. doi:10.1073/pnas.0500617102 PubMedCentralPubMedCrossRef Beilina A, Van Der Brug M, Ahmad R, Kesavapany S, Miller DW, Petsko GA, Cookson MR (2005) Mutations in PTEN-induced putative kinase 1 associated with recessive parkinsonism have differential effects on protein stability. Proc Natl Acad Sci U S A 102(16):5703–5708. doi:10.​1073/​pnas.​0500617102 PubMedCentralPubMedCrossRef
86.
go back to reference Deas E, Plun-Favreau H, Gandhi S, Desmond H, Kjaer S, Loh SH, Renton AE, Harvey RJ, Whitworth AJ, Martins LM, Abramov AY, Wood NW (2011) PINK1 cleavage at position A103 by the mitochondrial protease PARL. Hum Mol Genet 20(5):867–879. doi:10.1093/hmg/ddq526 PubMedCentralPubMedCrossRef Deas E, Plun-Favreau H, Gandhi S, Desmond H, Kjaer S, Loh SH, Renton AE, Harvey RJ, Whitworth AJ, Martins LM, Abramov AY, Wood NW (2011) PINK1 cleavage at position A103 by the mitochondrial protease PARL. Hum Mol Genet 20(5):867–879. doi:10.​1093/​hmg/​ddq526 PubMedCentralPubMedCrossRef
87.
go back to reference Lockhart PJ, Lincoln S, Hulihan M, Kachergus J, Wilkes K, Bisceglio G, Mash DC, Farrer MJ (2004) DJ-1 mutations are a rare cause of recessively inherited early onset parkinsonism mediated by loss of protein function. J Med Genet 41(3):e22PubMedCentralPubMedCrossRef Lockhart PJ, Lincoln S, Hulihan M, Kachergus J, Wilkes K, Bisceglio G, Mash DC, Farrer MJ (2004) DJ-1 mutations are a rare cause of recessively inherited early onset parkinsonism mediated by loss of protein function. J Med Genet 41(3):e22PubMedCentralPubMedCrossRef
89.
go back to reference Bonifati V, Rizzu P, Squitieri F, Krieger E, Vanacore N, van Swieten JC, Brice A, van Duijn CM, Oostra B, Meco G, Heutink P (2003) DJ-1( PARK7), a novel gene for autosomal recessive, early onset parkinsonism. Neurol Sci 24(3):159–160. doi:10.1007/s10072-003-0108-0 PubMedCrossRef Bonifati V, Rizzu P, Squitieri F, Krieger E, Vanacore N, van Swieten JC, Brice A, van Duijn CM, Oostra B, Meco G, Heutink P (2003) DJ-1( PARK7), a novel gene for autosomal recessive, early onset parkinsonism. Neurol Sci 24(3):159–160. doi:10.​1007/​s10072-003-0108-0 PubMedCrossRef
90.
go back to reference van Duijn CM, Dekker MC, Bonifati V, Galjaard RJ, Houwing-Duistermaat JJ, Snijders PJ, Testers L, Breedveld GJ, Horstink M, Sandkuijl LA, van Swieten JC, Oostra BA, Heutink P (2001) Park7, a novel locus for autosomal recessive early-onset parkinsonism, on chromosome 1p36. Am J Hum Genet 69(3):629–634. doi:10.1086/322996 PubMedCentralPubMedCrossRef van Duijn CM, Dekker MC, Bonifati V, Galjaard RJ, Houwing-Duistermaat JJ, Snijders PJ, Testers L, Breedveld GJ, Horstink M, Sandkuijl LA, van Swieten JC, Oostra BA, Heutink P (2001) Park7, a novel locus for autosomal recessive early-onset parkinsonism, on chromosome 1p36. Am J Hum Genet 69(3):629–634. doi:10.​1086/​322996 PubMedCentralPubMedCrossRef
92.
go back to reference Tarantino P, Civitelli D, Annesi F, De Marco EV, Rocca FE, Pugliese P, Nicoletti G, Carrideo S, Provenzano G, Annesi G, Quattrone A (2009) Compound heterozygosity in DJ-1 gene non-coding portion related to parkinsonism. Parkinsonism Relat Disord 15(4):324–326. doi:10.1016/j.parkreldis.2008.07.001 PubMedCrossRef Tarantino P, Civitelli D, Annesi F, De Marco EV, Rocca FE, Pugliese P, Nicoletti G, Carrideo S, Provenzano G, Annesi G, Quattrone A (2009) Compound heterozygosity in DJ-1 gene non-coding portion related to parkinsonism. Parkinsonism Relat Disord 15(4):324–326. doi:10.​1016/​j.​parkreldis.​2008.​07.​001 PubMedCrossRef
93.
go back to reference Hedrich K, Djarmati A, Schafer N, Hering R, Wellenbrock C, Weiss PH, Hilker R, Vieregge P, Ozelius LJ, Heutink P, Bonifati V, Schwinger E, Lang AE, Noth J, Bressman SB, Pramstaller PP, Riess O, Klein C (2004) DJ-1 (PARK7) mutations are less frequent than parkin (PARK2) mutations in early-onset Parkinson disease. Neurology 62(3):389–394PubMedCrossRef Hedrich K, Djarmati A, Schafer N, Hering R, Wellenbrock C, Weiss PH, Hilker R, Vieregge P, Ozelius LJ, Heutink P, Bonifati V, Schwinger E, Lang AE, Noth J, Bressman SB, Pramstaller PP, Riess O, Klein C (2004) DJ-1 (PARK7) mutations are less frequent than parkin (PARK2) mutations in early-onset Parkinson disease. Neurology 62(3):389–394PubMedCrossRef
94.
go back to reference Lev N, Roncevic D, Ickowicz D, Melamed E, Offen D (2006) Role of DJ-1 in Parkinson’s disease. J Mol Neurosci 29(3):215–225PubMedCrossRef Lev N, Roncevic D, Ickowicz D, Melamed E, Offen D (2006) Role of DJ-1 in Parkinson’s disease. J Mol Neurosci 29(3):215–225PubMedCrossRef
96.
go back to reference Xu J, Zhong N, Wang H, Elias JE, Kim CY, Woldman I, Pifl C, Gygi SP, Geula C, Yankner BA (2005) The Parkinson’s disease-associated DJ-1 protein is a transcriptional co-activator that protects against neuronal apoptosis. Hum Mol Genet 14(9):1231–1241. doi:10.1093/hmg/ddi134 PubMedCrossRef Xu J, Zhong N, Wang H, Elias JE, Kim CY, Woldman I, Pifl C, Gygi SP, Geula C, Yankner BA (2005) The Parkinson’s disease-associated DJ-1 protein is a transcriptional co-activator that protects against neuronal apoptosis. Hum Mol Genet 14(9):1231–1241. doi:10.​1093/​hmg/​ddi134 PubMedCrossRef
97.
go back to reference Bandopadhyay R, Kingsbury AE, Cookson MR, Reid AR, Evans IM, Hope AD, Pittman AM, Lashley T, Canet-Aviles R, Miller DW, McLendon C, Strand C, Leonard AJ, Abou-Sleiman PM, Healy DG, Ariga H, Wood NW, de Silva R, Revesz T, Hardy JA, Lees AJ (2004) The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson’s disease. Brain 127(Pt 2):420–430. doi:10.1093/brain/awh054 PubMedCrossRef Bandopadhyay R, Kingsbury AE, Cookson MR, Reid AR, Evans IM, Hope AD, Pittman AM, Lashley T, Canet-Aviles R, Miller DW, McLendon C, Strand C, Leonard AJ, Abou-Sleiman PM, Healy DG, Ariga H, Wood NW, de Silva R, Revesz T, Hardy JA, Lees AJ (2004) The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson’s disease. Brain 127(Pt 2):420–430. doi:10.​1093/​brain/​awh054 PubMedCrossRef
98.
go back to reference Besong Agbo D, Klafki H, Poschmann G, Seyfarth K, Genius J, Janssen C, Stuhler K, Wurst W, Meyer HE, Klingenspor M, Wiltfang J (2013) Development of a capillary isoelectric focusing immunoassay to measure DJ-1 isoforms in biological samples. Anal Biochem 443(2):197–204. doi:10.1016/j.ab.2013.09.013 PubMedCrossRef Besong Agbo D, Klafki H, Poschmann G, Seyfarth K, Genius J, Janssen C, Stuhler K, Wurst W, Meyer HE, Klingenspor M, Wiltfang J (2013) Development of a capillary isoelectric focusing immunoassay to measure DJ-1 isoforms in biological samples. Anal Biochem 443(2):197–204. doi:10.​1016/​j.​ab.​2013.​09.​013 PubMedCrossRef
99.
go back to reference Kumaran R, Kingsbury A, Coulter I, Lashley T, Williams D, de Silva R, Mann D, Revesz T, Lees A, Bandopadhyay R (2007) DJ-1 (PARK7) is associated with 3R and 4R tau neuronal and glial inclusions in neurodegenerative disorders. Neurobiol Dis 28(1):122–132. doi:10.1016/j.nbd.2007.07.012 PubMedCrossRef Kumaran R, Kingsbury A, Coulter I, Lashley T, Williams D, de Silva R, Mann D, Revesz T, Lees A, Bandopadhyay R (2007) DJ-1 (PARK7) is associated with 3R and 4R tau neuronal and glial inclusions in neurodegenerative disorders. Neurobiol Dis 28(1):122–132. doi:10.​1016/​j.​nbd.​2007.​07.​012 PubMedCrossRef
101.
go back to reference Lin X, Cook TJ, Zabetian CP, Leverenz JB, Peskind ER, Hu SC, Cain KC, Pan C, Edgar JS, Goodlett DR, Racette BA, Checkoway H, Montine TJ, Shi M, Zhang J (2012) DJ-1 isoforms in whole blood as potential biomarkers of Parkinson disease. Sci Rep 2:954. doi:10.1038/srep00954 PubMedCentralPubMed Lin X, Cook TJ, Zabetian CP, Leverenz JB, Peskind ER, Hu SC, Cain KC, Pan C, Edgar JS, Goodlett DR, Racette BA, Checkoway H, Montine TJ, Shi M, Zhang J (2012) DJ-1 isoforms in whole blood as potential biomarkers of Parkinson disease. Sci Rep 2:954. doi:10.​1038/​srep00954 PubMedCentralPubMed
102.
go back to reference Zhong N, Kim CY, Rizzu P, Geula C, Porter DR, Pothos EN, Squitieri F, Heutink P, Xu J (2006) DJ-1 transcriptionally up-regulates the human tyrosine hydroxylase by inhibiting the sumoylation of pyrimidine tract-binding protein-associated splicing factor. J Biol Chem 281(30):20940–20948. doi:10.1074/jbc.M601935200 PubMedCrossRef Zhong N, Kim CY, Rizzu P, Geula C, Porter DR, Pothos EN, Squitieri F, Heutink P, Xu J (2006) DJ-1 transcriptionally up-regulates the human tyrosine hydroxylase by inhibiting the sumoylation of pyrimidine tract-binding protein-associated splicing factor. J Biol Chem 281(30):20940–20948. doi:10.​1074/​jbc.​M601935200 PubMedCrossRef
103.
go back to reference Vilarino-Guell C, Soto AI, Lincoln SJ, Ben Yahmed S, Kefi M, Heckman MG, Hulihan MM, Chai H, Diehl NN, Amouri R, Rajput A, Mash DC, Dickson DW, Middleton LT, Gibson RA, Hentati F, Farrer MJ (2009) ATP13A2 variability in Parkinson disease. Hum Mutat 30(3):406–410. doi:10.1002/humu.20877 PubMedCentralPubMedCrossRef Vilarino-Guell C, Soto AI, Lincoln SJ, Ben Yahmed S, Kefi M, Heckman MG, Hulihan MM, Chai H, Diehl NN, Amouri R, Rajput A, Mash DC, Dickson DW, Middleton LT, Gibson RA, Hentati F, Farrer MJ (2009) ATP13A2 variability in Parkinson disease. Hum Mutat 30(3):406–410. doi:10.​1002/​humu.​20877 PubMedCentralPubMedCrossRef
105.
106.
go back to reference Lu CS, Lai SC, Wu RM, Weng YH, Huang CL, Chen RS, Chang HC, Wu-Chou YH, Yeh TH (2012) PLA2G6 mutations in PARK14-linked young-onset parkinsonism and sporadic Parkinson’s disease. Am J Med Genet B Neuropsychiatr Genet 159B(2):183–191. doi:10.1002/ajmg.b.32012 PubMedCrossRef Lu CS, Lai SC, Wu RM, Weng YH, Huang CL, Chen RS, Chang HC, Wu-Chou YH, Yeh TH (2012) PLA2G6 mutations in PARK14-linked young-onset parkinsonism and sporadic Parkinson’s disease. Am J Med Genet B Neuropsychiatr Genet 159B(2):183–191. doi:10.​1002/​ajmg.​b.​32012 PubMedCrossRef
107.
go back to reference Di Fonzo A, Dekker MC, Montagna P, Baruzzi A, Yonova EH, Correia Guedes L, Szczerbinska A, Zhao T, Dubbel-Hulsman LO, Wouters CH, de Graaff E, Oyen WJ, Simons EJ, Breedveld GJ, Oostra BA, Horstink MW, Bonifati V (2009) FBXO7 mutations cause autosomal recessive, early-onset parkinsonian-pyramidal syndrome. Neurology 72(3):240–245. doi:10.1212/01.wnl.0000338144.10967.2b PubMedCrossRef Di Fonzo A, Dekker MC, Montagna P, Baruzzi A, Yonova EH, Correia Guedes L, Szczerbinska A, Zhao T, Dubbel-Hulsman LO, Wouters CH, de Graaff E, Oyen WJ, Simons EJ, Breedveld GJ, Oostra BA, Horstink MW, Bonifati V (2009) FBXO7 mutations cause autosomal recessive, early-onset parkinsonian-pyramidal syndrome. Neurology 72(3):240–245. doi:10.​1212/​01.​wnl.​0000338144.​10967.​2b PubMedCrossRef
109.
go back to reference Gomez-Garre P, Jesus S, Carrillo F, Caceres-Redondo MT, Huertas-Fernandez I, Bernal-Bernal I, Bonilla-Toribio M, Vargas-Gonzalez L, Carballo M, Mir P (2014) Systematic mutational analysis of FBXO7 in a Parkinson’s disease population from southern Spain. Neurobiol Aging 35(3):727. e5–7. doi:10.1016/j.neurobiolaging.2013.09.011 Gomez-Garre P, Jesus S, Carrillo F, Caceres-Redondo MT, Huertas-Fernandez I, Bernal-Bernal I, Bonilla-Toribio M, Vargas-Gonzalez L, Carballo M, Mir P (2014) Systematic mutational analysis of FBXO7 in a Parkinson’s disease population from southern Spain. Neurobiol Aging 35(3):727. e5–7. doi:10.​1016/​j.​neurobiolaging.​2013.​09.​011
111.
113.
go back to reference Herzfeld T, Nolte D, Grznarova M, Hofmann A, Schultze JL, Muller U (2013) X-linked dystonia parkinsonism syndrome (XDP, lubag): disease-specific sequence change DSC3 in TAF1/DYT3 affects genes in vesicular transport and dopamine metabolism. Hum Mol Genet 22(5):941–951. doi:10.1093/hmg/dds499 PubMedCrossRef Herzfeld T, Nolte D, Grznarova M, Hofmann A, Schultze JL, Muller U (2013) X-linked dystonia parkinsonism syndrome (XDP, lubag): disease-specific sequence change DSC3 in TAF1/DYT3 affects genes in vesicular transport and dopamine metabolism. Hum Mol Genet 22(5):941–951. doi:10.​1093/​hmg/​dds499 PubMedCrossRef
114.
go back to reference Korvatska O, Strand NS, Berndt JD, Strovas T, Chen DH, Leverenz JB, Kiianitsa K, Mata IF, Karakoc E, Greenup JL, Bonkowski E, Chuang J, Moon RT, Eichler EE, Nickerson DA, Zabetian CP, Kraemer BC, Bird TD, Raskind WH (2013) Altered splicing of ATP6AP2 causes X-linked parkinsonism with spasticity (XPDS). Hum Mol Genet 22(16):3259–3268. doi:10.1093/hmg/ddt180 PubMedCentralPubMedCrossRef Korvatska O, Strand NS, Berndt JD, Strovas T, Chen DH, Leverenz JB, Kiianitsa K, Mata IF, Karakoc E, Greenup JL, Bonkowski E, Chuang J, Moon RT, Eichler EE, Nickerson DA, Zabetian CP, Kraemer BC, Bird TD, Raskind WH (2013) Altered splicing of ATP6AP2 causes X-linked parkinsonism with spasticity (XPDS). Hum Mol Genet 22(16):3259–3268. doi:10.​1093/​hmg/​ddt180 PubMedCentralPubMedCrossRef
116.
go back to reference Keyser RJ, Oppon E, Carr JA, Bardien S (2011) Identification of Parkinson’s disease candidate genes using CAESAR and screening of MAPT and SNCAIP in South African Parkinson’s disease patients. J Neural Transm 118(6):889–897. doi:10.1007/s00702-011-0591-z PubMedCrossRef Keyser RJ, Oppon E, Carr JA, Bardien S (2011) Identification of Parkinson’s disease candidate genes using CAESAR and screening of MAPT and SNCAIP in South African Parkinson’s disease patients. J Neural Transm 118(6):889–897. doi:10.​1007/​s00702-011-0591-z PubMedCrossRef
117.
go back to reference Marx FP, Holzmann C, Strauss KM, Li L, Eberhardt O, Gerhardt E, Cookson MR, Hernandez D, Farrer MJ, Kachergus J, Engelender S, Ross CA, Berger K, Schols L, Schulz JB, Riess O, Kruger R (2003) Identification and functional characterization of a novel R621C mutation in the synphilin-1 gene in Parkinson’s disease. Hum Mol Genet 12(11):1223–1231PubMedCrossRef Marx FP, Holzmann C, Strauss KM, Li L, Eberhardt O, Gerhardt E, Cookson MR, Hernandez D, Farrer MJ, Kachergus J, Engelender S, Ross CA, Berger K, Schols L, Schulz JB, Riess O, Kruger R (2003) Identification and functional characterization of a novel R621C mutation in the synphilin-1 gene in Parkinson’s disease. Hum Mol Genet 12(11):1223–1231PubMedCrossRef
118.
go back to reference Eyal A, Szargel R, Avraham E, Liani E, Haskin J, Rott R, Engelender S (2006) Synphilin-1A: an aggregation-prone isoform of synphilin-1 that causes neuronal death and is present in aggregates from alpha-synucleinopathy patients. Proc Natl Acad Sci U S A 103(15):5917–5922. doi:10.1073/pnas.0509707103 PubMedCentralPubMedCrossRef Eyal A, Szargel R, Avraham E, Liani E, Haskin J, Rott R, Engelender S (2006) Synphilin-1A: an aggregation-prone isoform of synphilin-1 that causes neuronal death and is present in aggregates from alpha-synucleinopathy patients. Proc Natl Acad Sci U S A 103(15):5917–5922. doi:10.​1073/​pnas.​0509707103 PubMedCentralPubMedCrossRef
119.
go back to reference Eyal A, Engelender S (2006) Synphilin isoforms and the search for a cellular model of Lewy body formation in Parkinson’s disease. Cell Cycle 5(18):2082–2086PubMedCrossRef Eyal A, Engelender S (2006) Synphilin isoforms and the search for a cellular model of Lewy body formation in Parkinson’s disease. Cell Cycle 5(18):2082–2086PubMedCrossRef
123.
go back to reference Svobodova E, Mrazova L, Luksan O, Elstein D, Zimran A, Stolnaya L, Minks J, Eberova J, Dvorakova L, Jirsa M, Hrebicek M (2011) Glucocerebrosidase gene has an alternative upstream promoter, which has features and expression characteristic of housekeeping genes. Blood Cells Mol Dis 46(3):239–245. doi:10.1016/j.bcmd.2010.12.011 PubMedCrossRef Svobodova E, Mrazova L, Luksan O, Elstein D, Zimran A, Stolnaya L, Minks J, Eberova J, Dvorakova L, Jirsa M, Hrebicek M (2011) Glucocerebrosidase gene has an alternative upstream promoter, which has features and expression characteristic of housekeeping genes. Blood Cells Mol Dis 46(3):239–245. doi:10.​1016/​j.​bcmd.​2010.​12.​011 PubMedCrossRef
125.
go back to reference Thomas T (2000) Monoamine oxidase-B inhibitors in the treatment of Alzheimer’s disease. Neurobiol Aging 21(2):343–348PubMedCrossRef Thomas T (2000) Monoamine oxidase-B inhibitors in the treatment of Alzheimer’s disease. Neurobiol Aging 21(2):343–348PubMedCrossRef
126.
go back to reference Stern G (1998) Neuroprotection by selegiline and other MAO inhibitors. J Neural Transm Suppl 52:99–107PubMedCrossRef Stern G (1998) Neuroprotection by selegiline and other MAO inhibitors. J Neural Transm Suppl 52:99–107PubMedCrossRef
129.
go back to reference Sobell JL, Lind TJ, Hebrink DD, Heston LL, Sommer SS (1997) Screening the monoamine oxidase B gene in 100 male patients with schizophrenia: a cluster of polymorphisms in African-Americans but lack of functionally significant sequence changes. Am J Med Genet 74(1):44–49PubMedCrossRef Sobell JL, Lind TJ, Hebrink DD, Heston LL, Sommer SS (1997) Screening the monoamine oxidase B gene in 100 male patients with schizophrenia: a cluster of polymorphisms in African-Americans but lack of functionally significant sequence changes. Am J Med Genet 74(1):44–49PubMedCrossRef
131.
go back to reference Stamper C, Siegel A, Liang WS, Pearson JV, Stephan DA, Shill H, Connor D, Caviness JN, Sabbagh M, Beach TG, Adler CH, Dunckley T (2008) Neuronal gene expression correlates of Parkinson’s disease with dementia. Mov Disord 23(11):1588–1595. doi:10.1002/mds.22184 PubMedCentralPubMedCrossRef Stamper C, Siegel A, Liang WS, Pearson JV, Stephan DA, Shill H, Connor D, Caviness JN, Sabbagh M, Beach TG, Adler CH, Dunckley T (2008) Neuronal gene expression correlates of Parkinson’s disease with dementia. Mov Disord 23(11):1588–1595. doi:10.​1002/​mds.​22184 PubMedCentralPubMedCrossRef
132.
135.
137.
go back to reference Soreq L, Salomonis N, Bronstein M, Greenberg DS, Israel Z, Bergman H, Soreq H (2013) Small RNA sequencing-microarray analyses in Parkinson leukocytes reveal deep brain stimulation-induced splicing changes that classify brain region transcriptomes. Front Mol Neurosci 6:10. doi:10.3389/fnmol.2013.00010 PubMedCentralPubMedCrossRef Soreq L, Salomonis N, Bronstein M, Greenberg DS, Israel Z, Bergman H, Soreq H (2013) Small RNA sequencing-microarray analyses in Parkinson leukocytes reveal deep brain stimulation-induced splicing changes that classify brain region transcriptomes. Front Mol Neurosci 6:10. doi:10.​3389/​fnmol.​2013.​00010 PubMedCentralPubMedCrossRef
Metadata
Title
Splicing: is there an alternative contribution to Parkinson’s disease?
Authors
Valentina La Cognata
Velia D’Agata
Francesca Cavalcanti
Sebastiano Cavallaro
Publication date
01-10-2015
Publisher
Springer Berlin Heidelberg
Published in
Neurogenetics / Issue 4/2015
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI
https://doi.org/10.1007/s10048-015-0449-x

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Acknowledgement to Referees

Acknowledgement to Referees 2014/2015