Comparative pathway and network analysis of brain transcriptome changes during adult aging and in Parkinson's disease

Neurobiology of Disease

Volumn 74, Issue , 2015, Pages 1-13

  Glaab, Enrico ^a   Schneider, Reinhard ^a  

^a UNIVERSITY OF LUXEMBOURG   (Luxembourg)

Author keywords

Aging; Biomarker; Meta analysis; Network analysis; Neurodegeneration; Omics; Parkinson's disease; Pathway analysis; Systems biology

Indexed keywords

BIOLOGICAL MARKER; NUCLEAR RECEPTOR RELATED FACTOR 1; TRANSCRIPTOME;

ADULT; AGED; AGING; ARTICLE; CASE CONTROL STUDY; CONTROLLED STUDY; DOWNSTREAM PROCESSING; GENE; GENE EXPRESSION; GENE MUTATION; GENETIC ASSOCIATION; HUMAN; NETWORK ANALYSIS; NEUROBIOLOGY; NR4A2 GENE; OXIDATIVE STRESS; PARKINSON DISEASE; PATHOGENESIS; PATHWAY ANALYSIS; RISK ASSESSMENT; TRANSCRIPTOMICS; COMPARATIVE STUDY; GENETICS; INFORMATION PROCESSING; META ANALYSIS; METABOLISM; MIDDLE AGED; SINGLE NUCLEOTIDE POLYMORPHISM; SUBSTANTIA NIGRA PARS COMPACTA; TISSUE MICROARRAY; YOUNG ADULT;

ADULT; AGING; BIOMARKERS; CASE-CONTROL STUDIES; DATASETS AS TOPIC; HUMANS; MIDDLE AGED; PARKINSON DISEASE; PARS COMPACTA; POLYMORPHISM, SINGLE NUCLEOTIDE; TISSUE ARRAY ANALYSIS; TRANSCRIPTOME; YOUNG ADULT;

EID: 84911899879     PISSN: 09699961     EISSN: 1095953X     Source Type: Journal    
DOI: 10.1016/j.nbd.2014.11.002     Document Type: Article

References (88)

1. Abou-Sleiman P.M., Muqit M.M., Wood N.W. Expanding insights of mitochondrial dysfunction in Parkinson's disease. Nat. Rev. Neurosci. 2006, 7(3):207-219.
2. Ambjørn M., Asmussen J.W., Lindstam M., Gotfryd K., Jacobsen C., Kiselyov V.V., Moestrup S.K., Penkowa M., Bock E., Berezin V. Metallothionein and a peptide modeled after metallothionein, EmtinB, induce neuronal differentiation and survival through binding to receptors of the low-density lipoprotein receptor family. J. Neurochem. 2008, 104(1):21-37.
3. Andrews G.K. Regulation of metallothionein gene expression by oxidative stress and metal ions. Biochem. Pharmacol. 2000, 59(1):95.
4. Araujo J., Breuer P., Dieringer S., Krauss S., Dorn S., Zimmermann K., Pfeifer A., Klockgether T., Wuellner U., Evert B.O. FOXO4-dependent upregulation of superoxide dismutase-2 in response to oxidative stress is impaired in spinocerebellar ataxia type 3. Hum. Mol. Genet. 2011, 20(15):2928-2941.
5. Arnould T., Vankoningsloo S., Renard P., Houbion A., Ninane N., Demazy C., Remacle J., Raes M. CREB activation induced by mitochondrial dysfunction is a new signaling pathway that impairs cell proliferation. EMBO J. 2002, 21(1):53-63.
6. Ashburner M., Ball C.A., Blake J.A., Botstein D., Butler H., Cherry J.M., Davis A.P., Dolinski K., Dwight S.S., Eppig J.T., Harris M.A., Hill D.P., Issel-Tarver L., Kasarskis A., Lewis S., Matese J.C., Richardson J.E., Ringwald M., Rubin G.M., Sherloc G. Gene Ontology: tool for the unification of biology. Nat. Genet. 2000, 25(1):25-29.
7. Barrett T., Troup D.B., Wilhite S.E., Ledoux P., Rudnev D., Evangelista C., Kim I.F., Soboleva A., Tomashevsky M., Marshall K.A., Phillippy K.H., Sherman P.M., Muertter R.N., Edgar R. NCBI GEO: archive for high-throughput functional genomic data. Nucleic Acids Res. 2009, 37(Suppl. 1):D885-D890.
8. Bender A., Krishnan K.J., Morris C.M., Taylor G.A., Reeve A.K., Perry R.H., Jaros E., Hersheson J.S., Betts J., Klopstock T., Taylor R.W., Turnbull D.M. High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat. Genet. 2006, 38(5):515-517.
9. Benjamini Y., Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. Ser. B Stat. Methodol. 1995, 289-300.
10. Blanpied T.A., Scott D.B., Ehlers M.D. Age-related regulation of dendritic endocytosis associated with altered clathrin dynamics. Neurobiol. Aging 2003, 24(8):1095-1104.
11. Bossi A., Lehner B. Tissue specificity and the human protein interaction network. Mol. Syst. Biol. 2009, 5(1).
12. Büeler H. Impaired mitochondrial dynamics and function in the pathogenesis of Parkinson's disease. Exp. Neurol. 2009, 218(2):235-246.
13. Calne D., McGeer E., Eisen A., Spencer P. Alzheimer's disease, Parkinson's disease, and motoneurone disease: abiotropic interaction between ageing and environment?. Lancet 1986, 328(8515):1067-1070.
14. Chae C.-H., Kim H.-T. Forced, moderate-intensity treadmill exercise suppresses apoptosis by increasing the level of NGF and stimulating phosphatidylinositol 3-kinase signaling in the hippocampus of induced aging rats. Neurochem. Int. 2009, 55(4):208-213.
15. Chartier-Harlin M.-C., Kachergus J., Roumier C., Mouroux V., Douay X., Lincoln S., Levecque C., Larvor L., Andrieux J., Hulihan M., Waucquier N., Defebvre L., Amouyel P., Farrer M., Destée A. alpha-Synuclein locus duplication as a cause of familial Parkinson's disease. Lancet 2004, 364(9440):1167-1169.
16. Chen Y., Cunningham F., Rios D., McLaren W.M., Smith J., Pritchard B., Spudich G.M., Brent S., Kulesha E., Marin-Garcia P., et al. Ensembl variation resources. BMC Genomics 2010, 11(1):293.
17. Cho J., Kim M., Kim K., Kim J. POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) inhibits endothelial cell senescence through a p53 dependent pathway. Cell Death Differ. 2011, 19(4):703-712.
18. Chu Y., Kompoliti K., Cochran E.J., Mufson E.J., Kordower J.H. Age-related decreases in Nurr1 immunoreactivity in the human substantia nigra. J. Comp. Neurol. 2002, 450(3):203-214.
19. Collier T.J., Kanaan N.M., Kordower J.H. Ageing as a primary risk factor for Parkinson's disease: evidence from studies of non-human primates. Nat. Rev. Neurosci. 2011, 12(6):359-366.
20. Do C.B., Tung J.Y., Dorfman E., Kiefer A.K., Drabant E.M., Francke U., Mountain J.L., Goldman S.M., Tanner C.M., Langston J.W., et al. Web-based genome-wide association study identifies two novel loci and a substantial genetic component for Parkinson's disease. PLoS Genet. 2011, 7(6):e1002141.
21. Foo J.-N., Liany H., Bei J.-X., Yu X.-Q., Liu J., Au W.-L., Prakash K.M., Tan L.C., Tan E.-K. A rare lysosomal enzyme gene SMPD1 variant (p. R591C) associates with Parkinson's disease. Neurobiol. Aging 2013, 34(12):e13.
22. Frey K.A., Koeppe R.A., Kilbourn M.R., Vander Borght T.M., Albin R.L., Gilman S., Kuhl D.E. Presynaptic monoaminergic vesicles in Parkinson's disease and normal aging. Ann. Neurol. 2004, 40(6):873-884.
23. Fuchs J., Nilsson C., Kachergus J., Munz M., Larsson E.-M., Schüle B., Langston J., Middleton F., Ross O., Hulihan M., Gasser T., Farrer M. Phenotypic variation in a large Swedish pedigree due to SNCA duplication and triplication. Neurology 2007, 68(12):916-922.
24. Fujita K.A., Ostaszewski M., Matsuoka Y., Ghosh S., Glaab E., Trefois C., Crespo I., Perumal T.M., Jurkowski W., Antony P.M.A., Diederich N., Buttini M., Kodama A., Satagopam V.P., Eifes S., Sol A., Schneider R., Kitano H., Balling R. Integrating pathways of Parkinson's disease in a molecular interaction map. Mol. Neurobiol. 2014, 49(1):88-102.
25. Gan-Or Z., Ozelius L.J., Bar-Shira A., Saunders-Pullman R., Mirelman A., Kornreich R., Gana-Weisz M., Raymond D., Rozenkrantz L., Deik A., et al. The p.L302P mutation in the lysosomal enzyme gene SMPD1 is a risk factor for Parkinson disease. Neurology 2013, 80(17):1606-1610.
26. Glaab E., Baudot A., Krasnogor N., Schneider R., Valencia A. EnrichNet: network-based gene set enrichment analysis. Bioinformatics 2012, 28(18):i451-i457.
27. Glatt S.J., Everall I.P., Kremen W.S., Corbeil J., Šášik R., Khanlou N., Han M., Liew C.-C., Tsuang M.T. Comparative gene expression analysis of blood and brain provides concurrent validation of SELENBP1 up-regulation in schizophrenia. Proc. Natl. Acad. Sci. U. S. A. 2005, 102(43):15533-15538.
28. Grimes D.A., Han F., Panisset M., Racacho L., Xiao F., Zou R., Westaff K., Bulman D.E. Translated mutation in the Nurr1 gene as a cause for Parkinson's disease. Mov. Disord. 2006, 21(7):906-909.
29. Hindle J.V. Ageing, neurodegeneration and Parkinson's disease. Age Ageing 2010, 39(2):156-161.
30. Ibanez P., Bonnet A., Debarges B., Lohmann E., Tison F., Pollak P., Agid Y., Dürr A., Brice A. Causal relation between alpha-synuclein locus duplication as a cause of familial Parkinson's disease. Lancet 2004, 364(9440):1169-1171.
31. Jiang C., Wan X., He Y., Pan T., Jankovic J., Le W. Age-dependent dopaminergic dysfunction in Nurr1 knockout mice. Exp. Neurol. 2005, 191(1):154-162.
32. Johnson M.B., Kawasawa Y.I., Mason C.E., Krsnik Ž., Coppola G., Bogdanović D., Geschwind D.H., Mane S.M., Šestan N. Functional and evolutionary insights into human brain development through global transcriptome analysis. Neuron 2009, 62(4):494-509.
33. Jones A.R., Overly C.C., Sunkin S.M. The Allen brain atlas: 5years and beyond. Nat. Rev. Neurosci. 2009, 10(11):821-828.
34. Joshi-Tope G., Gillespie M., Vastrik I., D'Eustachio P., Schmidt E., de Bono B., Jassal B., Gopinath G., Wu G., Matthews L., Lewis S., Birney E., Stein L. Reactome: a knowledgebase of biological pathways. Nucleic Acids Res. 2005, 33(Suppl. 1):D428-D432.
35. Kaasinen V., Rinne J.O. Functional imaging studies of dopamine system and cognition in normal aging and Parkinson's disease. Neurosci. Biobehav. Rev. 2002, 26(7):785-793.
36. Kadkhodaei B., Alvarsson A., Schintu N., Ramsköld D., Volakakis N., Joodmardi E., Yoshitake T., Kehr J., Decressac M., Björklund A., et al. Transcription factor Nurr1 maintains fiber integrity and nuclear-encoded mitochondrial gene expression in dopamine neurons. Proc. Natl. Acad. Sci. U. S. A. 2013, 110(6):2360-2365.
37. Kanehisa M., Goto S. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res. 2000, 28(1):27-30.
38. Kang H.J., Kawasawa Y.I., Cheng F., Zhu Y., Xu X., Li M., Sousa A.M., Pletikos M., Meyer K.A., Sedmak G., Guennel T., Shin Y., Johnson M.B., Krsnik Ž., Mayer S., Fertuzinhos S., Umlauf S., Lisgo S.N., Vortmeyer A., Weinberger S., Rand Mane Daniel, Hyde T.M., Huttner A., Reimers M., Kleinman J.E., Šestan N. Spatio-temporal transcriptome of the human brain. Nature 2011, 478(7370):483-489.
39. Kel A., Voss N., Jauregui R., Kel-Margoulis O., Wingender E. Beyond microarrays: finding key transcription factors controlling signal transduction pathways. BMC Bioinf. 2006, 7(Suppl. 2):S13.
40. Kumar A., Gibbs J.R., Beilina A., Dillman A., Kumaran R., Trabzuni D., Ryten M., Walker R., Smith C., Traynor B.J., Hardy J., Singleton A.B., Cookson M.R. Age-associated changes in gene expression in human brain and isolated neurons. Neurobiol. Aging 2013, 34(4):1199-1209.
41. Le W.-D., Conneely O.M., Zou L., He Y., Saucedo-Cardenas O., Jankovic J., Mosier D.R., Appel S.H. Selective agenesis of mesencephalic dopaminergic neurons in Nurr1-deficient mice. Exp. Neurol. 1999, 159(2):451-458.
42. Le W.-D., Conneely O.M., He Y., Jankovic J., Appel S.H. Reduced Nurr1 expression increases the vulnerability of mesencephalic dopamine neurons to MPTP-induced injury. J. Neurochem. 1999, 73:2218-2221.
43. Le W.-D., Xu P., Jankovic J., Jiang H., Appel S.H., Smith R.G., Vassilatis D.K. Mutations in NR4A2 associated with familial Parkinson disease. Nat. Genet. 2003, 33(1):85-89.
44. Lee J., Kim C.-H., Simon D.K., Aminova L.R., Andreyev A.Y., Kushnareva Y.E., Murphy A.N., Lonze B.E., Kim K.-S., Ginty D.D., Ferrante R.J., Ryu H., Ratan R.R. Mitochondrial cyclic AMP response element-binding protein (CREB) mediates mitochondrial gene expression and neuronal survival. J. Biol. Chem. 2005, 280(49):40398-40401.
45. Lein E.S., Hawrylycz M.J., Ao N., Ayres M., Bensinger A., Bernard A., Boe A.F., Boguski M.S., Brockway K.S., Byrnes E.J., Chen L., Chen L., Chen T.-M., Chin M.C., Chong J., Crook B.E., Czaplinska A., Dang C.N., Datta S., Dee N.R., Desaki A.L., Desta T., Diep E., Dolbeare T.A., Donelan M.J., Dong H.-W., Dougherty J.G., Duncan B.J., Ebbert A.J., Eichele G., et al. Genome-wide atlas of gene expression in the adult mouse brain. Nature 2006, 445(7124):168-176.
46. Lesage S., Brice A. Parkinson's disease: from monogenic forms to genetic susceptibility factors. Hum. Mol. Genet. 2009, 18(R1):R48-R59.
47. Lesnick T.G., Papapetropoulos S., Mash D.C., Ffrench-Mullen J., Shehadeh L., De Andrade M., Henley J.R., Rocca W.A., Ahlskog J.E., Maraganore D.M. A genomic pathway approach to a complex disease: axon guidance and Parkinson disease. PLoS Genet. 2007, 3(6):e98.
48. Levy G. The relationship of Parkinson disease with aging. Arch. Neurol. 2007, 64(9):1242.
49. Liu H., Tao Q., Deng H., Ming M., Ding Y., Xu P., Chen S., Song Z., Le W. Genetic analysis of NR4A2 gene in a large population of Han Chinese patients with Parkinson's disease. Eur. J. Neurol. 2013.
50. Marot G., Foulley J.-L., Mayer C.-D., Jaffrézic F. Moderated effect size and P-value combinations for microarray meta-analyses. Bioinformatics 2009, 25(20):2692-2699.
51. McGeer P.L., McGeer E.G. Inflammation and neurodegeneration in Parkinson's disease. Parkinsonism Relat. Disord. 2004, 10:S3-S7.
52. McGeer P., Itagaki S., Boyes B., McGeer E. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains. Neurology 1988, 38(8):1285.
53. Moran L., Duke D., Deprez M., Dexter D., Pearce R.K., Graeber M. Whole genome expression profiling of the medial and lateral substantia nigra in Parkinson's disease. Neurogenetics 2006, 7(1):1-11.
54. Naoi M., Maruyama W. Cell death of dopamine neurons in aging and Parkinson's disease. Mech. Ageing Dev. 1999, 111(2):175-188.
55. Nichols W.C., Uniacke S.K., Pankratz N., Reed T., Simon D.K., Halter C., Rudolph A., Shults C.W., Conneally P.M., Foroud T. Evaluation of the role of Nurr1 in a large sample of familial Parkinson's disease. Mov. Disord. 2004, 19(6):649-655.
56. Nikitin A., Egorov S., Daraselia N., Mazo I. Pathway studio-the analysis and navigation of molecular networks. Bioinformatics 2003, 19(16):2155-2157.
57. Nixon R.A. Endosome function and dysfunction in Alzheimer's disease and other neurodegenerative diseases. Neurobiol. Aging 2005, 26(3):373-382.
58. Olmea O., Rost B., Valencia A. Effective use of sequence correlation and conservation in fold recognition. J. Mol. Biol. 1999, 293(5):1221-1239.
59. 11C] DOPA. Life Sci. 2006, 79(8):730-736.
60. Pan T., Kondo S., Le W., Jankovic J. The role of autophagy-lysosome pathway in neurodegeneration associated with Parkinson's disease. Brain 2008, 131(8):1969-1978.
61. Paz J., Yao H., Lim H.S., Lu X.-Y., Zhang W. The neuroprotective role of attractin in neurodegeneration. Neurobiol. Aging 2007, 28(9):1446-1456.
62. Pico A.R., Kelder T., van Iersel M.P., Hanspers K., Conklin B.R., Evelo C. WikiPathways: pathway editing for the people. PLoS Biol. 2008, 6(7):e184.
63. Qian L., Flood P.M., Hong J.-S. Neuroinflammation is a key player in Parkinson's disease and a prime target for therapy. J. Neural Transm. 2010, 117(8):971-979.
64. Sacchetti P., Carpentier R., Ségard P., Olivé-Cren C., Lefebvre P. Multiple signaling pathways regulate the transcriptional activity of the orphan nuclear receptor NURR1. Nucleic Acids Res. 2006, 34(19):5515-5527.
65. Saijo K., Winner B., Carson C.T., Collier J.G., Boyer L., Rosenfeld M.G., Gage F.H., Glass C.K. A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell 2009, 137(1):47-59.
66. Scatton B., Javoy-Agid F., Rouquier L., Dubois B., Agid Y. Reduction of cortical dopamine, noradrenaline, serotonin and their metabolites in Parkinson's disease. Brain Res. 1983, 275(2):321-328.
67. Shadrina M., Slominsky P., Limborska S. Molecular mechanisms of pathogenesis of Parkinson's disease. J. Pediatr. Matern. Fam. Health Chiropr. 2010, 281:229.
68. Sharma S., Ebadi M. Metallothioneins as early and sensitive biomarkers of redox signalling in neurodegenerative disorders. IIOAB J. 2011, 2:98-106.
69. Sherer T.B., Richardson J.R., Testa C.M., Seo B.B., Panov A.V., Yagi T., Matsuno-Yagi A., Miller G.W., Greenamyre J.T. Mechanism of toxicity of pesticides acting at complex I: relevance to environmental etiologies of Parkinson's disease. J. Neurochem. 2007, 100(6):1469-1479.
70. Shin N., Jeong H., Kwon J., Heo H.Y., Kwon J.J., Yun H.J., Kim C.-H., Han B.S., Tong Y., Shen J., Hatano T., Hattori N., Kim K.-S., Changa S., Seol W. LRRK2 regulates synaptic vesicle endocytosis. Exp. Cell Res. 2008, 314(10):2055-2065.
71. Simunovic F., Yi M., Wang Y., Macey L., Brown L.T., Krichevsky A.M., Andersen S.L., Stephens R.M., Benes F.M., Sonntag K.C. Gene expression profiling of substantia nigra dopamine neurons: further insights into Parkinson's disease pathology. Brain 2009, 132(7):1795-1809.
72. Sleiman P., Healy D., Muqit M., Yang Y., Van Der Brug M., Holton J., Revesz T., Quinn N., Bhatia K., Diss J., Lees A., Cookson D., Latchman M.R., Wood N. Characterisation of a novel NR4A2 mutation in Parkinson's disease brain. Neurosci. Lett. 2009, 457(2):75-79.
73. Smyth G.K. Linear models and empirical Bayes methods for assessing differential expression in microarray experiments. Stat. Appl. Genet. Mol. Biol. 2004, 3(1):3.
74. Soper J.H., Kehm V., Burd C.G., Bankaitis V.A., Lee V.M.-Y. Aggregation of α-synuclein in S. cerevisiae is associated with defects in endosomal trafficking and phospholipid biosynthesis. J. Mol. Neurosci. 2011, 43(3):391-405.
75. Su A.I., Wiltshire T., Batalov S., Lapp H., Ching K.A., Block D., Zhang J., Soden R., Hayakawa M., Kreiman G., Cooke M.P., Walker J.R., Hogenesch J.B. A gene atlas of the mouse and human protein-encoding transcriptomes. Proc. Natl. Acad. Sci. U. S. A. 2004, 101(16):6062-6067.
76. Tan E.-K., Chung H., Chandran V.R., Tan C., Shen H., Yew K., Pavanni R., Puvan K.-A., Wong M.-C., Teoh M.-L., Yih Y., Zhao Y. Nurr1 mutational screen in Parkinson's disease. Mov. Disord. 2004, 19(12):1503-1505.
77. Tong H., Faloutsos C., Pan J.-Y. Random walk with restart: fast solutions and applications. Knowl. Inf. Syst. 2008, 14(3):327-346.
78. Tusher V.G., Tibshirani R., Chu G. Significance analysis of microarrays applied to the ionizing radiation response. Proc. Natl. Acad. Sci. U. S. A. 2001, 98(9):5116-5121.
79. Watson M. CoXpress: differential co-expression in gene expression data. BMC Bioinf. 2006, 7(1):509.
80. Wu Z., Irizarry R.A., Gentleman R., Martinez-Murillo F., Spencer F. A model-based background adjustment for oligonucleotide expression arrays. J. Am. Stat. Assoc. 2004, 909-917.
81. Xu P.-Y., Liang R., Jankovic J., Hunter C., Zeng Y.-X., Ashizawa T., Lai D., Le W.-D. Association of homozygous 7048G7049 variant in the intron six of Nurr1 gene with Parkinson's disease. Neurology 2002, 58(6):881-884.
82. Yang Y.X., Latchman D.S. Nurr1 transcriptionally regulates the expression of alpha-synuclein. Neuroreport 2008, 19(8):867-871.
83. Zetterström R.H., Solomin L., Jansson L., Hoffer B.J., Olson L., Perlmann T. Dopamine neuron agenesis in Nurr1-deficient mice. Science 1997, 276(5310):248-250.
84. Zhang Y., James M., Middleton F.A., Davis R.L. Transcriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms. Am. J. Med. Genet. B 2005, 137(1):5-16.
85. Zhang B., Gaiteri C., Bodea L.-G., Wang Z., McElwee J., Podtelezhnikov A.A., Zhang C., Xie T., Tran L., Dobrin R., et al. Integrated systems approach identifies genetic nodes and networks in late-onset Alzheimer's disease. Cell 2013, 153(3):707-720.
86. Zheng K., Heydari B., Simon D.K. A common NURR1 polymorphism associated with Parkinson disease and diffuse Lewy body disease. Arch. Neurol. 2003, 60(5):722.
87. Zheng B., Liao Z., Locascio J.J., Lesniak K.A., Roderick S.S., Watt M.L., Eklund A.C., Zhang-James Y., Kim P.D., Hauser M.A., et al. PGC-1α, a potential therapeutic target for early intervention in Parkinson's disease. Sci. Transl. Med. 2010, 2(52):52ra73.
88. Zimprich A., Asmus F., Leitner P., Castro M., Bereznai B., Homann N., Ott E., Rutgers A.W., Wieditz G., Trenkwalder C., Gasser T. Point mutations in exon 1 of the NR4A2 gene are not a major cause of familial Parkinson's disease. Neurogenetics 2003, 4(4):219-220.