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. 2012 Sep 5;3(3):319–326. doi: 10.1016/j.nurx.2006.05.008

Microarrays in Parkinson’s disease: A systematic approach

Renee M Miller 1, Howard J Federoff 1,2,
PMCID: PMC3593377  PMID: 16815215

Summary

Neurological disease (ND) is one of the greatest challenges facing our population, from medical, financial, and social perspectives. The application of new research approaches to understand the underlying pathogenesis of ND is critical. In this article, we review the use of microarray analysis in Parkinson’s disease (PD). Microarrays have tremendous power, simultaneously querying the expression of tens of thousands of genes from a given biological sample. Coupled with impressive advances in statistical tools for analyzing large, complex data sets, well-designed microarray experiments are poised to make a big impact in the field of ND. Parkinson’s disease is a devastating neurodegenerative disease well suited to a systems-based microarray analysis. Genetic and environmental rodent models of PD emulate many of the cardinal features of human PD, providing the unique opportunity to compare gene expression profiles from different etiologies of the same disease. The elucidation of important gene expression patterns during disease will make possible identification of genetic susceptibility markers, biomarkers of disease progression, and new therapeutic targets.

Key Words: Microarray, Parkinson’s disease, human, MPTP, α-synuclein, gene expression

References

  • 1.Maguire-Zeiss KA, Federoff HJ. Convergent pathobiologic model of Parkinson’s disease. Ann NY Acad Sci. 2003;991:152–166. doi: 10.1111/j.1749-6632.2003.tb07473.x. [DOI] [PubMed] [Google Scholar]
  • 2.Bezard E, Gross CE, Founder MC, Dovero S, Bloch B, Jaber M. Absence of MPTP-induced neuronal death in mice lacking the dopamine transporter. Exp Neurol. 1999;155:268–273. doi: 10.1006/exnr.1998.6995. [DOI] [PubMed] [Google Scholar]
  • 3.Gainetdinov RR, Fumagalli F, Jones SR, Caron MG. Dopamine transporter is required for in vivo MPTP neurotoxicity: evidence from mice lacking the transporter. J Neurochem. 1997;69:1322–1325. doi: 10.1046/j.1471-4159.1997.69031322.x. [DOI] [PubMed] [Google Scholar]
  • 4.Gainetdinov RR, Fumagalli F, Wang YM, Jones SR, Levey AI, Miller GW, et al. Increased MPTP neurotoxicity in vesicular monoamine transporter 2 heterozygote knockout mice. J Neurochem. 1998;70:1973–1978. doi: 10.1046/j.1471-4159.1998.70051973.x. [DOI] [PubMed] [Google Scholar]
  • 5.Teismann P, Tieu K, Cohen O, Choi DK, Wu du C, Marks D, et al. Pathogenic role of glial cells in Parkinson’s disease. Mov Disord. 2003;18:121–129. doi: 10.1002/mds.10332. [DOI] [PubMed] [Google Scholar]
  • 6.Perez FA, Curtis WR, Palmiter RD. Parkin-deficient mice are not more sensitive to 6-hydroxydopamine or methamphetamine neurotoxicity. BMC Neurosci. 2005;6:71–71. doi: 10.1186/1471-2202-6-71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Fomai F, Schluter OM, Lenzi P, Gesi M, Ruffoli R, Ferrucci M, et al. Parkinson-like syndrome induced by continuous MPTP infusion: convergent roles of the ubiquitin-proteasome system and alpha-synuclein. Proc Natl Acad Sci USA. 2005;102:3413–3418. doi: 10.1073/pnas.0409713102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Galvin JE, Lee VM, Trojanowski JQ. Synucleinopathies: clinical and pathological implications. Arch Neurol. 2001;58:186–190. doi: 10.1001/archneur.58.2.186. [DOI] [PubMed] [Google Scholar]
  • 9.Fleming SM, Femagut PO, Chesselet MF. Genetic mouse models of parkinsonism: strengths and limitations. NeuroRx. 2005;2:495–503. doi: 10.1602/neurorx.2.3.495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Bove J, Prou D, Perier C, Przedborski S. Toxin-induced models of Parkinson’s disease. NeuroRx. 2005;2:484–494. doi: 10.1602/neurorx.2.3.484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Ginsberg SD, Che S, Counts SE, Mufson EJ. Single cell gene expression profiling in Alzheimer’s disease. NeuroRx. 2006;3:302–317. doi: 10.1016/j.nurx.2006.05.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Olson NE. The microarray data analysis process: from raw data to biological significance. NeuroRx. 2006;3:371–381. doi: 10.1016/j.nurx.2006.05.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Almudevar A, Klebanov LB, Qiu X, Salzman P, Yakovlev AY. Utility of correlation measures in analysis of gene expression. NeuroRx. 2006;3:382–393. doi: 10.1016/j.nurx.2006.05.037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Fathallah-Shaykh HM. Microarrays: applications and pitfalls. Arch Neurol. 2005;62:1669–1672. doi: 10.1001/archneur.62.11.1669. [DOI] [PubMed] [Google Scholar]
  • 15.Blalock EM, Chen KC, Stromberg AJ, Norris CM, Kadish I, Kraner SD, et al. Harnessing the power of gene microarrays for the study of brain aging and Alzheimer’s disease: statistical reliability and functional correlation. Aging Res Rev. 2005;4:481–512. doi: 10.1016/j.arr.2005.06.006. [DOI] [PubMed] [Google Scholar]
  • 16.Colangelo V, Schurr J, Ball MJ, Pelaez RP, Bazan NG, Lukiw WJ. Gene expression profiling of 12633 genes in Alzheimer hippocampal CA1: transcription and neurotrophic factor down-regulation and up-regulation of apoptotic and pro-inflammatory signaling. J Neurosci Res. 2002;70:462–473. doi: 10.1002/jnr.10351. [DOI] [PubMed] [Google Scholar]
  • 17.Loring JF, Wen X, Lee JM, Seilhamer J, Somogyi R. A gene expression profile of Alzheimer’s disease. DNA Cell Biol. 2001;20:683–695. doi: 10.1089/10445490152717541. [DOI] [PubMed] [Google Scholar]
  • 18.Dangond F, Hwang D, Camelo S, Pasinelli P, Frosch MP, Stephanopoulos G, et al. Molecular signature of late-stage human ALS revealed by expression profiling of postmortem spinal cord gray matter. Physiol Genomics. 2004;16:229–239. doi: 10.1152/physiolgenomics.00087.2001. [DOI] [PubMed] [Google Scholar]
  • 19.Jiang YM, Yamamoto M, Kobayashi Y, Yoshihara T, Liang Y, Terao S, et al. Gene expression profile of spinal motor neurons in sporadic amyotrophic lateral sclerosis. Ann Neurol. 2005;57:236–251. doi: 10.1002/ana.20379. [DOI] [PubMed] [Google Scholar]
  • 20.Chan EY, Luthi-Carter R, Strand A, Solano SM, Hanson SA, DeJohn MM, et al. Increased huntingtin protein length reduces the number of polyglutamine-induced gene expression changes in mouse models of Huntington’s disease. Hum Mol Genet. 2002;11:1939–1951. doi: 10.1093/hmg/11.17.1939. [DOI] [PubMed] [Google Scholar]
  • 21.Borovecki F, Lovrecic L, Zhou J, Jeong H, Then F, Rosas HD, et al. Genome-wide expression profiling of human blood reveals biomarkers for Huntington’s disease. Proc Natl Acad Sci USA. 2005;102:11023–11028. doi: 10.1073/pnas.0504921102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Strand AD, Aragaki AK, Shaw D, Bird T, Holton J, Turner C, et al. Gene expression in Huntington’s disease skeletal muscle: a potential biomarker. Hum Mol Genet. 2005;14:1863–1876. doi: 10.1093/hmg/ddi192. [DOI] [PubMed] [Google Scholar]
  • 23.Grunblatt E, Mandel S, Maor G, Youdim MB. Gene expression analysis in N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mice model of Parkinson’s disease using cDNA microarray: effect of R-apomorphine. J Neurochem. 2001;78:1–12. doi: 10.1046/j.1471-4159.2001.00397.x. [DOI] [PubMed] [Google Scholar]
  • 24.Miller RM, Callahan LM, Casaceli C, Chen L, Riser GL, Chui B, et al. Dysregulation of gene expression in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse substantia nigra. J Neurosci. 2004;24:7445–7454. doi: 10.1523/JNEUROSCI.4204-03.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Miller RM, Chen LL, Riser GL, Giesler TL, Kaysser-Kranich TM, Palaniappan C, et al. Temporal evolution of mouse striatal gene expression following MPTP injury. Neurobiol Aging. 2005;26:765–775. doi: 10.1016/j.neurobiolaging.2004.12.002. [DOI] [PubMed] [Google Scholar]
  • 26.Napolitano M, Centonze D, Calce A, Picconi B, Spiezia S, Gulino A, et al. Experimental parkinsonism modulates multiple genes involved in the transduction of dopaminergic signals in the striatum. Neurobiol Dis. 2002;10:387–395. doi: 10.1006/nbdi.2002.0525. [DOI] [PubMed] [Google Scholar]
  • 27.Schwarting RK, Huston JP. Unilateral 6-hydroxydopamine lesions of meso-striatal dopamine neurons and their physiological sequelae. Prog Neurobiol. 1996;49:215–266. doi: 10.1016/S0301-0082(96)00015-9. [DOI] [PubMed] [Google Scholar]
  • 28.Schultz W. Depletion of dopamine in the striatum as an experimental model of Parkinsonism: direct effects and adaptive mechanisms. Prog Neurobiol. 1982;18:121–166. doi: 10.1016/0301-0082(82)90015-6. [DOI] [PubMed] [Google Scholar]
  • 29.Holtz WA, O’ Malley KL. Parkinsonian mimetics induce aspects of unfolded protein response in death of dopaminergic neurons. J Biol Chem. 2003;278:19367–19377. doi: 10.1074/jbc.M211821200. [DOI] [PubMed] [Google Scholar]
  • 30.Yoo MS, Chun HS, Son JJ, DeGiorgio LA, Kim DJ, Peng C, et al. Oxidative stress regulated genes in nigral dopaminergic neuronal cells: correlation with the known pathology in Parkinson’s disease. Brain Res Mol Brain Res. 2003;110:76–84. doi: 10.1016/S0169-328X(02)00586-7. [DOI] [PubMed] [Google Scholar]
  • 31.Chun HS, Gibson GE, DeGiorgio LA, Zhang H, Kidd VJ, Son JH. Dopaminergic cell death induced by MPP(+), oxidant and specific neurotoxicants shares the common molecular mechanism. J Neurochem. 2001;76:1010–1021. doi: 10.1046/j.1471-4159.2001.00096.x. [DOI] [PubMed] [Google Scholar]
  • 32.Scherzer CR, Jensen RV, Gullans SR, Feany MB. Gene expression changes presage neurodegeneration in aDrosophila model of Parkinson’s disease. Hum Mol Genet. 2003;12:2457–2466. doi: 10.1093/hmg/ddg265. [DOI] [PubMed] [Google Scholar]
  • 33.Hauser MA, Li YJ, Xu H, Noureddine MA, Shao YS, Gullans SR, et al. Expression profiling of substantia nigra in Parkinson’s disease, progressive supranuclear palsy, and frontotemporal dementia with parkinsonism. Arch Neurol. 2005;62:917–921. doi: 10.1001/archneur.62.6.917. [DOI] [PubMed] [Google Scholar]
  • 34.Grunblatt E, Mandel S, Jacob-Hirsch J, Zeligson S, Amariglo N, Rechavi G, et al. Gene expression profiling of parkinsonian substantia nigra pars compacta: alterations in ubiquitin-proteasome, heat shock protein, iron and oxidative stress regulated proteins, cell adhesion/cellular matrix and vesicle trafficking genes. J Neural Transm. 2004;111:1543–1573. doi: 10.1007/s00702-004-0212-1. [DOI] [PubMed] [Google Scholar]
  • 35.Miller RM, Riser GL, Kaysser-Kranich TM, Lockner RJ, Palaniappan C, Federoff HJ. Robust dysregulation of gene expression in substantia nigra and striatum in Parkinson’s disease. Neurobiol Dis. 2006;21:305–313. doi: 10.1016/j.nbd.2005.07.010. [DOI] [PubMed] [Google Scholar]
  • 36.Miller RM, Federoff HJ. Altered gene expression profiles reveal similarities and differences between Parkinson’s disease and model systems. Neuroscientist. 2005;11:539–549. doi: 10.1177/1073858405278330. [DOI] [PubMed] [Google Scholar]
  • 37.Erlanson-Albertsson C. Uncoupling proteins: a new family of proteins with unknown function. Nutr Neurosci. 2002;5:1–11. doi: 10.1080/10284150290007038. [DOI] [PubMed] [Google Scholar]
  • 38.Ermak G, Cheadle C, Becker KG, Harris CD, Davies RJ. DSCR1(Adapt78) modulates expression of SOD1. FASEB J. 2004;18:62–69. doi: 10.1096/fj.03-0451com. [DOI] [PubMed] [Google Scholar]
  • 39.Simon HH, Saueressig H, Wurst W, Goulding MD, O’Leary DD. Fate of midbrain dopaminergic neurons controlled by the engrailed genes. J Neurosci. 2001;21:3126–3134. doi: 10.1523/JNEUROSCI.21-09-03126.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Simon HH, Bhatt L, Gherbassi D, Sgado P, Alberi L. Midbrain dopaminergic neurons: determination of their developmental fate by transcription factors. Ann NY Acad Sci. 2003;991:36–47. doi: 10.1111/j.1749-6632.2003.tb07461.x. [DOI] [PubMed] [Google Scholar]

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