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BioMed Research International
Volume 2014, Article ID 543673, 16 pages
http://dx.doi.org/10.1155/2014/543673
Research Article

Complex Network-Driven View of Genomic Mechanisms Underlying Parkinson’s Disease: Analyses in Dorsal Motor Vagal Nucleus, Locus Coeruleus, and Substantia Nigra

1Department of Pediatrics, Faculdade de Medicina da USP (FMUSP), Avenida Dr. Enéas Carvalho Aguiar 647, 5 Andar, 05403-900 São Paulo, SP, Brazil
2Brazilian Aging Brain Study Group (BEHEEC), LIM 22, FMUSP, 01246-903 São Paulo, SP, Brazil
3Hospital Israelita Albert Einstein, 05652-900 São Paulo, SP, Brazil
4Division of Geriatrics, FMUSP, 01246-903 São Paulo, SP, Brazil
5Department of Pathology, FMUSP, 01246-903 São Paulo, SP, Brazil
6Department of Neurology and Pathology, University of California, San Francisco, CA 94143, USA

Received 28 May 2014; Accepted 15 September 2014; Published 26 November 2014

Academic Editor: Meike Kasten

Copyright © 2014 Beatriz Raposo Corradini et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. A. H. V. Schapira, “Neurobiology and treatment of Parkinson's disease,” Trends in Pharmacological Sciences, vol. 30, no. 1, pp. 41–47, 2009. View at Publisher · View at Google Scholar · View at Scopus
  2. O. Corti, S. Lesage, and A. Brice, “What genetics tells us about the causes and mechanisms of Parkinson's disease,” Physiological Reviews, vol. 91, no. 4, pp. 1161–1218, 2011. View at Publisher · View at Google Scholar · View at Scopus
  3. A. E. Kingsbury, R. Bandopadhyay, L. Silveira-Moriyama et al., “Brain stem pathology in Parkinson's disease: an evaluation of the Braak staging model,” Movement Disorders, vol. 25, no. 15, pp. 2508–2515, 2010. View at Publisher · View at Google Scholar · View at Scopus
  4. C. Hansen and J. Y. Li, “Beyond α-synuclein transfer: pathology propagation in Parkinson's disease,” Trends in Molecular Medicine, vol. 18, no. 5, pp. 248–255, 2012. View at Publisher · View at Google Scholar · View at Scopus
  5. H. Braak, K. Del Tredici, U. Rüb, R. A. I. de Vos, E. N. H. J. Steur, and E. Braak, “Staging of brain pathology related to sporadic Parkinson's disease,” Neurobiology of Aging, vol. 24, no. 2, pp. 197–211, 2003. View at Publisher · View at Google Scholar · View at Scopus
  6. H. Braak, U. Rüb, W. P. Gai, and K. Del Tredici, “Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen,” Journal of Neural Transmission, vol. 110, no. 5, pp. 517–536, 2003. View at Publisher · View at Google Scholar · View at Scopus
  7. C. J. R. Dunning, J. F. Reyes, J. A. Steiner, and P. Brundin, “Can Parkinson's disease pathology be propagated from one neuron to another?” Progress in Neurobiology, vol. 97, no. 2, pp. 205–219, 2012. View at Publisher · View at Google Scholar · View at Scopus
  8. O. Marques and T. F. Outeiro, “Alpha-synuclein: from secretion to dysfunction and death,” Cell Death and Disease, vol. 3, no. 7, article e350, 2012. View at Publisher · View at Google Scholar · View at Scopus
  9. J. G. Greene, “Current status and future directions of gene expression profiling in Parkinson's disease,” Neurobiology of Disease, vol. 45, no. 1, pp. 76–82, 2012. View at Publisher · View at Google Scholar · View at Scopus
  10. P. A. Lewis and M. R. Cookson, “Gene expression in the Parkinson's disease brain,” Brain Research Bulletin, vol. 88, no. 4, pp. 302–312, 2012. View at Publisher · View at Google Scholar · View at Scopus
  11. S. W. Scholz, T. Mhyre, H. Ressom, S. Shah, and H. J. Federoff, “Genomics and bioinformatics of Parkinson's disease,” Cold Spring Harbor Perspectives in Medicine, vol. 2, no. 7, Article ID a009449, 2012. View at Publisher · View at Google Scholar · View at Scopus
  12. T. Ideker and N. J. Krogan, “Differential network biology,” Molecular Systems Biology, vol. 8, article 565, 2012. View at Publisher · View at Google Scholar · View at Scopus
  13. Y. J. Edwards, G. W. Beecham, W. K. Scott et al., “Identifying consensus disease pathways in Parkinson's disease using an integrative systems biology approach,” PLoS ONE, vol. 6, no. 2, Article ID e16917, 2011. View at Publisher · View at Google Scholar · View at Scopus
  14. H. E. S. Marei, A. Althani, N. Afifi et al., “Gene expression profiling of embryonic human neural stem cells and dopaminergic neurons from adult human substantia nigra,” PLoS ONE, vol. 6, no. 12, Article ID e28420, 2011. View at Publisher · View at Google Scholar · View at Scopus
  15. J. J. Cai, E. Borenstein, and D. A. Petrov, “Broker genes in human disease,” Genome Biology and Evolution, vol. 2, pp. 815–825, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. S. Chavali, F. Barrenas, K. Kanduri, and M. Benson, “Network properties of human disease genes with pleiotropic effects,” BMC Systems Biology, vol. 4, article 78, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. A.-L. Barabasi, N. Gulbahce, and J. Loscalzo, “Network medicine: a network-based approach to human disease,” Nature Reviews Genetics, vol. 12, no. 1, pp. 56–68, 2011. View at Publisher · View at Google Scholar · View at Scopus
  18. D. Chaussabel and N. Baldwin, “Democratizing systems immunology with modular transcriptional repertoire analyses,” Nature Reviews Immunology, vol. 14, no. 4, pp. 271–280, 2014. View at Publisher · View at Google Scholar · View at Scopus
  19. S. Y. Bando, F. N. Silva, L. D. F. Costa et al., “Complex network analysis of CA3 transcriptome reveals pathogenic and compensatory pathways in refractory temporal lobe epilepsy,” PLoS ONE, vol. 8, no. 11, Article ID e79913, 2013. View at Publisher · View at Google Scholar · View at Scopus
  20. C. Gaiteri, Y. Ding, B. French, G. C. Tseng, and E. Sibille, “Beyond modules and hubs: the potential of gene coexpression networks for investigating molecular mechanisms of complex brain disorders,” Genes, Brain and Behavior, vol. 13, no. 1, pp. 13–24, 2014. View at Publisher · View at Google Scholar · View at Scopus
  21. L. T. Grinberg, R. E. Lucena Ferretti, J. M. Farfel et al., “Brain bank of the Brazilian aging brain study group—a milestone reached and more than 1,600 collected brains,” Cell and Tissue Banking, vol. 8, no. 2, pp. 151–162, 2007. View at Publisher · View at Google Scholar · View at Scopus
  22. L. Opitz, G. Salinas-Riester, M. Grade et al., “Impact of RNA degradation on gene expression profiling,” BMC Medical Genomics, vol. 3, article 36, 2010. View at Publisher · View at Google Scholar · View at Scopus
  23. M. T. Weirauch, “Gene expression network for the analysis of cDNA microarray data,” in Applied Statistics for Network Biology: Methods in Systems Biology, M. Dehmer, F. Emmert-Streib, A. Graber, and A. Salvador, Eds., vol. 1, pp. 215–250, Wiley-Blackwell, Weinheim, Germany, 2011. View at Google Scholar
  24. M. E. J. Newman, Networks: An Introduction, Oxford University Press, New York, NY, USA, 2010. View at Publisher · View at Google Scholar · View at MathSciNet
  25. C. P. Marquez and E. J. Pritham, “Phantom, a new subclass of Mutator DNA transposons found in insect viruses and widely distributed in animals,” Genetics, vol. 185, no. 4, pp. 1507–1517, 2010. View at Publisher · View at Google Scholar · View at Scopus
  26. C. D. Arvanitis, M. Bazan-Peregrino, B. Rifai, L. W. Seymour, and C. C. Coussios, “Cavitation-enhanced extravasation for drug delivery,” Ultrasound in Medicine and Biology, vol. 37, no. 11, pp. 1838–1852, 2011. View at Publisher · View at Google Scholar · View at Scopus
  27. O. Dmytriyeva, S. Pankratova, S. Owczarek et al., “The metastasis-promoting S100A4 protein confers neuroprotection in brain injury,” Nature Communications, vol. 3, article 1197, 2012. View at Publisher · View at Google Scholar · View at Scopus
  28. M. Moldovan, V. Pinchenko, O. Dmytriyeva et al., “Peptide mimetic of the S100A4 protein modulates peripheral nerve regeneration and attenuates the progression of neuropathy in myelin protein P0 null mice,” Molecular Medicine, vol. 19, no. 1, pp. 43–53, 2013. View at Publisher · View at Google Scholar · View at Scopus
  29. M. S. Müller, R. Fox, A. Schousboe, H. S. Waagepetersen, and L. K. Bak, “Astrocyte glycogenolysis is triggered by store-operated calcium entry and provides metabolic energy for cellular calcium homeostasis,” GLIA, vol. 62, no. 4, pp. 526–534, 2014. View at Publisher · View at Google Scholar · View at Scopus
  30. Y. Zhang, X. Yu, M. Ichikawa et al., “Autosomal recessive phosphoglucomutase 3 (PGM3) mutations link glycosylation defects to atopy, immune deficiency, autoimmunity, and neurocognitive impairment,” Journal of Allergy and Clinical Immunology, vol. 133, no. 5, pp. 1400–1409, 2014. View at Publisher · View at Google Scholar · View at Scopus
  31. J. Hornig, F. Fröb, M. R. Vogl, I. Hermans-Borgmeyer, E. R. Tamm, and M. Wegner, “The transcription factors Sox10 and Myrf define an essential regulatory network module in differentiating oligodendrocytes,” PLoS Genetics, vol. 9, no. 10, Article ID e1003907, 2013. View at Publisher · View at Google Scholar · View at Scopus
  32. T. Nakayama, T. Yaoi, and G. Kuwajima, “Localization and subcellular distribution of N-copine in mouse brain,” Journal of Neurochemistry, vol. 72, no. 1, pp. 373–379, 1999. View at Publisher · View at Google Scholar · View at Scopus
  33. K. Rogowski, J. van Dijk, M. M. Magiera et al., “A family of protein-deglutamylating enzymes associated with neurodegeneration,” Cell, vol. 143, no. 4, pp. 564–578, 2010. View at Publisher · View at Google Scholar · View at Scopus
  34. A. Louvi and E. A. Grove, “Cilia in the CNS: the quiet organelle claims center stage,” Neuron, vol. 69, no. 6, pp. 1046–1060, 2011. View at Publisher · View at Google Scholar · View at Scopus
  35. E. Rybnikova, T. Gluschenko, A. Galeeva et al., “Differential expression of ADAM15 and ADAM17 metalloproteases in the rat brain after severe hypobaric hypoxia and hypoxic preconditioning,” Neuroscience Research, vol. 72, no. 4, pp. 364–373, 2012. View at Publisher · View at Google Scholar · View at Scopus
  36. F. Ikeda, Y. L. Deribe, S. S. Skånland et al., “SHARPIN forms a linear ubiquitin ligase complex regulating NF-κB activity and apoptosis,” Nature, vol. 471, no. 7340, pp. 637–641, 2011. View at Publisher · View at Google Scholar · View at Scopus
  37. Z. Wang, C. S. Potter, J. P. Sundberg, and H. Hogenesch, “SHARPIN is a key regulator of immune and inflammatory responses,” Journal of Cellular and Molecular Medicine, vol. 16, no. 10, pp. 2271–2279, 2012. View at Publisher · View at Google Scholar · View at Scopus
  38. F. Tokunaga, “Linear ubiquitination-mediated NF-κB regulation and its related disorders,” Journal of Biochemistry, vol. 154, no. 4, pp. 313–323, 2013. View at Publisher · View at Google Scholar · View at Scopus
  39. L. Meng, J. K. Hsu, and R. Y. L. Tsai, “GNL3L depletion destabilizes MDM2 and induces p53-dependent G2/M arrest,” Oncogene, vol. 30, no. 14, pp. 1716–1726, 2011. View at Publisher · View at Google Scholar · View at Scopus
  40. T. Engel, A. Sanz-Rodgriguez, E. M. Jimenez-Mateos et al., “CHOP regulates the p53-MDM2 axis and is required for neuronal survival after seizures,” Brain, vol. 136, no. 2, pp. 577–592, 2013. View at Publisher · View at Google Scholar · View at Scopus
  41. A. Palanca, I. Casafont, M. T. Berciano, and M. Lafarga, “Reactive nucleolar and Cajal body responses to proteasome inhibition in sensory ganglion neurons,” Biochimica et Biophysica Acta: Molecular Basis of Disease, vol. 1842, no. 6, pp. 848–859, 2014. View at Publisher · View at Google Scholar · View at Scopus
  42. C. Andreu-Agullo, T. Maurin, C. B. Thompson, and E. C. Lai, “Ars2 maintains neural stem-cell identity through direct transcriptional activation of Sox2,” Nature, vol. 481, no. 7380, pp. 195–198, 2012. View at Publisher · View at Google Scholar · View at Scopus
  43. R. M. Adibhatla and J. F. Hatcher, “Phospholipase A2, reactive oxygen species, and lipid peroxidation in CNS pathologies,” BMB Reports, vol. 41, no. 8, pp. 560–567, 2008. View at Publisher · View at Google Scholar
  44. V. Bonifati, “Genetics of Parkinson's disease—state of the art, 2013,” Parkinsonism and Related Disorders, vol. 20, supplement 1, pp. S23–S28, 2014. View at Publisher · View at Google Scholar · View at Scopus
  45. N. Kurabayashi, M. D. Nguyen, and K. Sanada, “The G protein-coupled receptor GPRC5B contributes to neurogenesis in the developing mouse neocortex,” Development (Cambridge), vol. 140, no. 21, pp. 4335–4346, 2013. View at Publisher · View at Google Scholar · View at Scopus
  46. P. J. Harrison, L. Lyon, L. J. Sartorius, P. W. J. Burnet, and T. A. Lane, “The group II metabotropic glutamate receptor 3 (mGluR3, mGlu3, GRM3): expression, function and involvement in schizophrenia,” Journal of Psychopharmacology, vol. 22, no. 3, pp. 308–322, 2008. View at Publisher · View at Google Scholar · View at Scopus
  47. J. Mounce, L. Luo, A. Caprihan, J. Liu, N. I. Perrone-Bizzozero, and V. D. Calhoun, “Association of GRM3 polymorphism with white matter integrity in schizophrenia,” Schizophrenia Research, vol. 155, no. 1–3, pp. 8–14, 2014. View at Publisher · View at Google Scholar · View at Scopus
  48. D. Jantas, A. Greda, S. Golda et al., “Neuroprotective effects of metabotropic glutamate receptor group II and III activators against MPP(+)-induced cell death in human neuroblastoma SH-SY5Y cells: the impact of cell differentiation state,” Neuropharmacology, vol. 83, pp. 36–53, 2014. View at Publisher · View at Google Scholar · View at Scopus
  49. J. C. Dugas, Y. C. Tai, T. P. Speed, J. Ngai, and B. A. Barres, “Functional genomic analysis of oligodendrocyte differentiation,” Journal of Neuroscience, vol. 26, no. 43, pp. 10967–10983, 2006. View at Publisher · View at Google Scholar · View at Scopus
  50. A. M. Manzardo, S. Gunewardena, and M. G. Butler, “Over-expression of the miRNA cluster at chromosome 14q32 in the alcoholic brain correlates with suppression of predicted target mRNA required for oligodendrocyte proliferation,” Gene, vol. 526, no. 2, pp. 356–363, 2013. View at Publisher · View at Google Scholar · View at Scopus
  51. A. G. McLennan, “The Nudix hydrolase superfamily,” Cellular and Molecular Life Sciences, vol. 63, no. 2, pp. 123–143, 2006. View at Publisher · View at Google Scholar · View at Scopus
  52. H. Steinbrenner and H. Sies, “Selenium homeostasis and antioxidant selenoproteins in brain: implications for disorders in the central nervous system,” Archives of Biochemistry and Biophysics, vol. 536, no. 2, pp. 152–157, 2013. View at Publisher · View at Google Scholar · View at Scopus
  53. M. H. Nisancioglu, W. M. Mahoney Jr., D. D. Kimmel, S. M. Schwartz, C. Betsholtz, and G. Genové, “Generation and characterization of rgs5 mutant mice,” Molecular and Cellular Biology, vol. 28, no. 7, pp. 2324–2331, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. B. Stieglitz, L. F. Haire, I. Dikic, and K. Rittinger, “Structural analysis of SHARPIN, a subunit of a large multi-protein E3 ubiquitin ligase, reveals a novel dimerization function for the pleckstrin homology superfold,” The Journal of Biological Chemistry, vol. 287, no. 25, pp. 20823–20829, 2012. View at Publisher · View at Google Scholar · View at Scopus
  55. J. Zhu, J. Gardner, C. R. Pullinger, J. P. Kane, J. F. Thompson, and O. L. Francone, “Regulation of apoAI processing by procollagen C-proteinase enhancer-2 and bone morphogenetic protein-1,” Journal of Lipid Research, vol. 50, no. 7, pp. 1330–1339, 2009. View at Publisher · View at Google Scholar · View at Scopus
  56. K. Toyo-oka, D. Mori, Y. Yano et al., “Protein phosphatase 4 catalytic subunit regulates Cdk1 activity and microtubule organization via NDEL1 dephosphorylation,” The Journal of Cell Biology, vol. 180, no. 6, pp. 1133–1147, 2008. View at Publisher · View at Google Scholar · View at Scopus
  57. M. Terashima, M. Kobayashi, M. Motomiya et al., “Analysis of the expression and function of BRINP family genes during neuronal differentiation in mouse embryonic stem cell-derived neural stem cells,” Journal of Neuroscience Research, vol. 88, no. 7, pp. 1387–1393, 2010. View at Publisher · View at Google Scholar · View at Scopus
  58. P. Krebs, W. Fan, Y.-H. Chen et al., “Lethal mitochondrial cardiomyopathy in a hypomorphic Med30 mouse mutant is ameliorated by ketogenic diet,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 49, pp. 19678–19682, 2011. View at Publisher · View at Google Scholar · View at Scopus
  59. G. Corrente, D. Guardavaccaro, and F. Tirone, “PC3 potentiates NGF-induced differentiation and protects neurons from apoptosis,” NeuroReport, vol. 13, no. 4, pp. 417–422, 2002. View at Publisher · View at Google Scholar · View at Scopus
  60. N. Ezzeddine, C.-Y. A. Chen, and A.-B. Shyu, “Evidence providing new insights into TOB-promoted deadenylation and supporting a link between TOB's deadenylation-enhancing and antiproliferative activities,” Molecular and Cellular Biology, vol. 32, no. 6, pp. 1089–1098, 2012. View at Publisher · View at Google Scholar · View at Scopus
  61. H.-X. Hao, Y. Xie, Y. Zhang et al., “ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner,” Nature, vol. 484, no. 7397, pp. 195–200, 2012. View at Publisher · View at Google Scholar · View at Scopus
  62. S. A. Purro, S. Galli, and P. C. Salinas, “Dysfunction of Wnt signaling and synaptic disassembly in neurodegenerative diseases,” Journal of Molecular Cell Biology, vol. 6, no. 1, pp. 75–80, 2014. View at Publisher · View at Google Scholar · View at Scopus
  63. F. L'Episcopo, C. Tirolo, S. Caniglia et al., “Targeting Wnt signaling at the neuroimmune interface for dopaminergic neuroprotection/repair in Parkinson's disease,” Journal of Molecular Cell Biology, vol. 6, no. 1, pp. 13–26, 2014. View at Publisher · View at Google Scholar · View at Scopus
  64. J. A. Papalas, N. N. Balmer, C. Wallace, and O. P. Sangüeza, “Ossifying dermatofibroma with osteoclast-like giant cells: report of a case and literature review,” American Journal of Dermatopathology, vol. 31, no. 4, pp. 379–383, 2009. View at Publisher · View at Google Scholar · View at Scopus
  65. C. Yamashita, H. Tomiyama, M. Funayama et al., “The evaluation of polyglutamine repeats in autosomal dominant Parkinson's disease,” Neurobiology of Aging, vol. 35, no. 7, pp. 1779.e17–1779.e21, 2014. View at Publisher · View at Google Scholar · View at Scopus
  66. F. Pelisch, J. Gerez, J. Druker et al., “The serine/arginine-rich protein SF2/ASF regulates protein sumoylation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 37, pp. 16119–16124, 2010. View at Publisher · View at Google Scholar · View at Scopus
  67. P. Krumova, E. Meulmeester, M. Garrido et al., “Sumoylation inhibits α-synuclein aggregation and toxicity,” The Journal of Cell Biology, vol. 194, no. 1, pp. 49–60, 2011. View at Publisher · View at Google Scholar · View at Scopus
  68. B. T. Huang, P. Y. Chang, C. H. Su, C. C. Chao, and S. Lin-Chao, “Gas7-deficient mouse reveals roles in motor function and muscle fiber composition during aging,” PLoS ONE, vol. 7, no. 5, Article ID e37702, 2012. View at Publisher · View at Google Scholar
  69. A. Gotoh, M. Hidaka, K. Hirose, and T. Uchida, “Gas7b (growth arrest specific protein 7b) regulates neuronal cell morphology by enhancing microtubule and actin filament assembly,” Journal of Biological Chemistry, vol. 288, no. 48, pp. 34699–34706, 2013. View at Publisher · View at Google Scholar · View at Scopus
  70. N. Kumamoto, Y. Gu, J. Wang et al., “A role for primary cilia in glutamatergic synaptic integration of adult-born neurons,” Nature Neuroscience, vol. 15, no. 3, pp. 399–405, 2012. View at Publisher · View at Google Scholar · View at Scopus
  71. S. M. Guadiana, S. Semple-Rowland, D. Daroszewski et al., “Arborization of dendrites by developing neocortical neurons is dependent on primary cilia and type 3 adenylyl cyclase,” The Journal of Neuroscience, vol. 33, no. 6, pp. 2626–2638, 2013. View at Publisher · View at Google Scholar · View at Scopus
  72. Q. Weng, Y. Chen, H. Wang et al., “Dual-mode modulation of Smad signaling by Smad -interacting protein Sip1 is required for myelination in the central nervous system,” Neuron, vol. 73, no. 4, pp. 713–728, 2012. View at Publisher · View at Google Scholar · View at Scopus
  73. G. L. McKinsey, S. Lindtner, B. Trzcinski et al., “Dlx1&2-dependent expression of Zfhx1b (Sip1, Zeb2) regulates the fate switch between cortical and striatal interneurons,” Neuron, vol. 77, no. 1, pp. 83–98, 2013. View at Publisher · View at Google Scholar · View at Scopus
  74. N. Goldenberg-Cohen, A. Raiter, V. Gaydar et al., “Peptide-binding GRP78 protects neurons from hypoxia-induced apoptosis,” Apoptosis, vol. 17, no. 3, pp. 278–288, 2012. View at Publisher · View at Google Scholar · View at Scopus
  75. H. J. Chung, J. D. Kim, K. H. Kim, and N. Y. Jeong, “G protein-coupled receptor, family C, group 5 (GPRC5B) downregulation in spinal cord neurons is involved in neuropathic pain,” Korean Journal of Anesthesiology, vol. 66, no. 3, pp. 230–236, 2014. View at Publisher · View at Google Scholar · View at Scopus
  76. A. C. Paula-Lima, M. A. Tricerri, J. Brito-Moreira et al., “Human apolipoprotein A-I binds amyloid-β and prevents Aβ-induced neurotoxicity,” The International Journal of Biochemistry and Cell Biology, vol. 41, no. 6, pp. 1361–1370, 2009. View at Publisher · View at Google Scholar · View at Scopus
  77. G. D. Stanwood, J. P. Parlaman, and P. Levitt, “Genetic or pharmacological inactivation of the dopamine D1 receptor differentially alters the expression of regulator of G-protein signalling (Rgs) transcripts,” The European Journal of Neuroscience, vol. 24, no. 3, pp. 806–818, 2006. View at Publisher · View at Google Scholar · View at Scopus
  78. A.-C. Luissint, C. Artus, F. Glacial, K. Ganeshamoorthy, and P.-O. Couraud, “Tight junctions at the blood brain barrier: Physiological architecture and disease-associated dysregulation,” Fluids and Barriers of the CNS, vol. 9, no. 1, article 23, 2012. View at Publisher · View at Google Scholar · View at Scopus
  79. A. Venkatraman, Y. S. Hu, A. Didonna et al., “The histone deacetylase HDAC3 is essential for Purkinje cell function, potentially complicating the use of HDAC inhibitors in SCA1,” Human Molecular Genetics, vol. 23, no. 14, pp. 3733–3745, 2014. View at Publisher · View at Google Scholar
  80. X. Zhang, Y. Ozawa, H. Lee et al., “Histone deacetylase 3 (HDAC3) activity is regulated by interaction with protein serine/threonine phosphatase 4,” Genes and Development, vol. 19, no. 7, pp. 827–839, 2005. View at Publisher · View at Google Scholar · View at Scopus
  81. I. F. Harrison and D. T. Dexter, “Epigenetic targeting of histone deacetylase: therapeutic potential in Parkinson's disease?” Pharmacology and Therapeutics, vol. 140, no. 1, pp. 34–52, 2013. View at Publisher · View at Google Scholar · View at Scopus
  82. A. Z. Herskovits and L. Guarente, “SIRT1 in neurodevelopment and brain senescence,” Neuron, vol. 81, no. 3, pp. 471–483, 2014. View at Publisher · View at Google Scholar · View at Scopus
  83. G. Mudò, J. Mäkelä, V. Di Liberto et al., “Transgenic expression and activation of PGC-1α protect dopaminergic neurons in the MPTP mouse model of Parkinsons disease,” Cellular and Molecular Life Sciences, vol. 69, no. 7, pp. 1153–1165, 2012. View at Publisher · View at Google Scholar · View at Scopus
  84. Y. You, W. Li, Y. Gong et al., “ShcD interacts with TrkB via its PTB and SH2 domains and regulates BDNF-induced MAPK activation,” BMB Reports, vol. 43, no. 7, pp. 485–490, 2010. View at Publisher · View at Google Scholar · View at Scopus
  85. M. E. Fenner, C. L. Achim, and B. M. Fenner, “Expression of full-length and truncated trkB in human striatum and substantia nigra neurons: Implications for Parkinson's disease,” Journal of Molecular Histology, vol. 45, no. 3, pp. 349–361, 2014. View at Publisher · View at Google Scholar · View at Scopus
  86. F. Ma, C. Zhang, K. V. S. Prasad, G. J. Freeman, and S. F. Schlossman, “Molecular cloning of porimin, a novel cell surface receptor mediating oncotic cell death,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 17, pp. 9778–9783, 2001. View at Publisher · View at Google Scholar · View at Scopus
  87. A. Vejux and G. Lizard, “Cytotoxic effects of oxysterols associated with human diseases: induction of cell death (apoptosis and/or oncosis), oxidative and inflammatory activities, and phospholipidosis,” Molecular Aspects of Medicine, vol. 30, no. 3, pp. 153–170, 2009. View at Publisher · View at Google Scholar · View at Scopus
  88. A. Rosello, G. Warnes, and U. C. Meier, “Cell death pathways and autophagy in the central nervous system and its involvement in neurodegeneration, immunity and central nervous system infection: to die or not to die—that is the question,” Clinical and Experimental Immunology, vol. 168, no. 1, pp. 52–57, 2012. View at Publisher · View at Google Scholar · View at Scopus
  89. G. G. Perrone, C. M. Grant, and I. W. Dawes, “Genetic and environmental factors influencing glutathione homeostasis in Saccharomyces cerevisiae,” Molecular Biology of the Cell, vol. 16, no. 1, pp. 218–230, 2005. View at Publisher · View at Google Scholar · View at Scopus
  90. M. A. Joshi, N. H. Jeoung, M. Obayashi et al., “Impaired growth and neurological abnormalities in branched-chain α-keto acid dehydrogenase kinase-deficient mice,” Biochemical Journal, vol. 400, no. 1, pp. 153–162, 2006. View at Publisher · View at Google Scholar · View at Scopus
  91. Z. Li, S. M. Lukasik, Y. Liu et al., “A mutation in the S-switch region of the Runt domain alters the dynamics of an allosteric network responsible for CBF beta regulation,” Journal of Molecular Biology, vol. 364, no. 5, pp. 1073–1083, 2006. View at Publisher · View at Google Scholar · View at Scopus
  92. K.-I. Inoue, T. Shiga, and Y. Ito, “Runx transcription factors in neuronal development,” Neural Development, vol. 3, article 20, 2008. View at Publisher · View at Google Scholar · View at Scopus
  93. Y. X. Chao, B. P. He, and S. S. W. Tay, “Mesenchymal stem cell transplantation attenuates blood brain barrier damage and neuroinflammation and protects dopaminergic neurons against MPTP toxicity in the substantia nigra in a model of Parkinson's disease,” Journal of Neuroimmunology, vol. 216, no. 1-2, pp. 39–50, 2009. View at Publisher · View at Google Scholar · View at Scopus
  94. Y. Eshed, K. Feinberg, S. Poliak et al., “Gliomedin mediates Schwann cell-axon interaction and the molecular assembly of the nodes of Ranvier,” Neuron, vol. 47, no. 2, pp. 215–229, 2005. View at Publisher · View at Google Scholar · View at Scopus
  95. K. Feinberg, Y. Eshed-Eisenbach, S. Frechter et al., “A glial signal consisting of gliomedin and NrCAM clusters axonal Na+ channels during the formation of nodes of Ranvier,” Neuron, vol. 65, no. 4, pp. 490–502, 2010. View at Publisher · View at Google Scholar · View at Scopus
  96. R. Bonasio, E. Lecona, and D. Reinberg, “MBT domain proteins in development and disease,” Seminars in Cell and Developmental Biology, vol. 21, no. 2, pp. 221–230, 2010. View at Publisher · View at Google Scholar · View at Scopus
  97. A. Dahiya, S. Wong, S. Gonzalo, M. Gavin, and D. C. Dean, “Linking the Rb and Polycomb pathways,” Molecular Cell, vol. 8, no. 3, pp. 557–569, 2001. View at Publisher · View at Google Scholar · View at Scopus
  98. M.-Y. Wu, T.-F. Tsai, and A. L. Beaudet, “Deficiency of Rbbp1/Arid4a and Rbbp1l1/Arid4b alters epigenetic modifications and suppresses an imprinting defect in the PWS/AS domain,” Genes and Development, vol. 20, no. 20, pp. 2859–2870, 2006. View at Publisher · View at Google Scholar · View at Scopus
  99. P. Korhonen, T. Tapiola, T. Suuronen, and A. Salminen, “Expression of transcriptional repressor protein mSin3A but not mSin3B is induced during neuronal apoptosis,” Biochemical and Biophysical Research Communications, vol. 252, no. 1, pp. 274–277, 1998. View at Publisher · View at Google Scholar · View at Scopus
  100. J. Katahira, T. Miki, K. Takano et al., “Nuclear RNA export factor 7 is localized in processing bodies and neuronal RNA granules through interactions with shuttling hnRNPs,” Nucleic Acids Research, vol. 36, no. 2, pp. 616–628, 2008. View at Publisher · View at Google Scholar · View at Scopus
  101. P. Jansen, K. Giehl, J. R. Nyengaard et al., “Roles for the pro-neurotrophin receptor sortilin in neuronal development, aging and brain injury,” Nature Neuroscience, vol. 10, no. 11, pp. 1449–1457, 2007. View at Publisher · View at Google Scholar · View at Scopus
  102. S. Capsoni, G. Amato, D. Vignone, C. Criscuolo, A. Nykjaer, and A. Cattaneo, “Dissecting the role of sortilin receptor signaling in neurodegeneration induced by NGF deprivation,” Biochemical and Biophysical Research Communications, vol. 431, no. 3, pp. 579–585, 2013. View at Publisher · View at Google Scholar · View at Scopus
  103. L. C. Xia, D. Ai, J. Cram, J. A. Fuhrman, and F. Sun, “Efficient statistical significance approximation for local similarity analysis of high-throughput time series data,” Bioinformatics, vol. 29, no. 2, pp. 230–237, 2013. View at Publisher · View at Google Scholar · View at Scopus
  104. P. C. Holm, F. J. Rodríguez, J. Kele, G. Castelo-Branco, J. Kitajewski, and E. Arenas, “BMPs, FGF8 and Wnts regulate the differentiation of locus coeruleus noradrenergic neuronal precursors,” Journal of Neurochemistry, vol. 99, no. 1, pp. 343–352, 2006. View at Publisher · View at Google Scholar · View at Scopus
  105. R. Bajo-Grañeras, M. D. Ganfornina, E. Martín-Tejedor, and D. Sanchez, “Apolipoprotein D mediates autocrine protection of astrocytes and controls their reactivity level, contributing to the functional maintenance of paraquat-challenged dopaminergic systems,” Glia, vol. 59, no. 10, pp. 1551–1566, 2011. View at Publisher · View at Google Scholar · View at Scopus
  106. R. Bajo-Grañeras, D. Sanchez, G. Gutierrez et al., “Apolipoprotein D alters the early transcriptional response to oxidative stress in the adult cerebellum,” Journal of Neurochemistry, vol. 117, no. 6, pp. 949–960, 2011. View at Publisher · View at Google Scholar · View at Scopus
  107. D. Domenger, D. Dea, L. Theroux, L. Moquin, A. Gratton, and J. Poirier, “The MPTP neurotoxic lesion model of Parkinson's disease activates the apolipoprotein E cascade in the mouse brain,” Experimental Neurology, vol. 233, no. 1, pp. 513–522, 2012. View at Publisher · View at Google Scholar · View at Scopus
  108. V. G. Khaindrava, E. A. Kozina, V. S. Kudrin et al., “Experimental modeling of preclinical and clinical stages of Parkinson's disease,” Bulletin of Experimental Biology and Medicine, vol. 150, no. 5, pp. 566–569, 2011. View at Publisher · View at Google Scholar · View at Scopus
  109. R. Nandhagopal, L. Kuramoto, M. Schulzer et al., “Longitudinal evolution of compensatory changes in striatal dopamine processing in Parkinson's disease,” Brain, vol. 134, no. 11, pp. 3290–3298, 2011. View at Publisher · View at Google Scholar · View at Scopus
  110. B. Sampaio-Marques, C. Felgueiras, A. Silva et al., “SNCA (α-synuclein)-induced toxicity in yeast cells is dependent on sirtuin 2 (Sir2)-mediated mitophagy,” Autophagy, vol. 8, no. 10, pp. 1494–1509, 2012. View at Publisher · View at Google Scholar · View at Scopus
  111. A. Nykjaer and T. E. Willnow, “Sortilin: a receptor to regulate neuronal viability and function,” Trends in Neurosciences, vol. 35, no. 4, pp. 261–270, 2012. View at Publisher · View at Google Scholar · View at Scopus
  112. R. D. Perea, R. C. Rada, J. Wilson et al., “A comparative white matter study with Parkinson's disease, Parkinson's disease with Dementia and Alzheimer's Disease,” Journal of Alzheimer's & Disease Parkinsonism, vol. 3, article 123, 2014. View at Google Scholar
  113. J. Eryilmaz, P. Pan, M. F. Amaya et al., “Structural studies of a four-MBT repeat protein MBTD1,” PLoS ONE, vol. 4, no. 10, Article ID e7274, 2009. View at Publisher · View at Google Scholar · View at Scopus
  114. G. U. Höglinger, J. J. Breunig, C. Depboylu et al., “The pRb/E2F cell-cycle pathway mediates cell death in Parkinson's disease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 9, pp. 3585–3590, 2007. View at Publisher · View at Google Scholar · View at Scopus
  115. M. Ramaswami, J. P. Taylor, and R. Parker, “Altered ribostasis: RNA-protein granules in degenerative disorders,” Cell, vol. 154, no. 4, pp. 727–736, 2013. View at Publisher · View at Google Scholar · View at Scopus
  116. T. Vanderweyde, K. Youmans, L. Liu-Yesucevitz, and B. Wolozin, “Role of stress granules and RNA-binding proteins in neurodegeneration: a mini-review,” Gerontology, vol. 59, no. 6, pp. 524–533, 2013. View at Publisher · View at Google Scholar · View at Scopus
  117. O. Binda, C. Nassif, and P. E. Branton, “SIRT1 negatively regulates HDAC1-dependent transcriptional repression by the RBP1 family of proteins,” Oncogene, vol. 27, no. 24, pp. 3384–3392, 2008. View at Publisher · View at Google Scholar · View at Scopus
  118. L. Parkkinen, T. Pirttilâ, and I. Alafuzoff, “Applicability of current staging/categorization of α-synuclein pathology and their clinical relevance,” Acta Neuropathologica, vol. 115, no. 4, pp. 399–407, 2008. View at Publisher · View at Google Scholar · View at Scopus
  119. J. A. Obeso, M. C. Rodriguez-Oroz, C. G. Goetz et al., “Molecular cloning of porimin, a novel cell surface receptor mediating oncotic cell death,” Nature Medicine, vol. 16, no. 6, pp. 653–661, 2010. View at Publisher · View at Google Scholar · View at Scopus
  120. A. H. Schapira and P. Jenner, “Etiology and pathogenesis of Parkinson's disease,” Movement Disorders, vol. 26, no. 6, pp. 1049–1055, 2011. View at Publisher · View at Google Scholar · View at Scopus
  121. I. Ferrer, A. Martinez, R. Blanco, E. Dalfó, and M. Carmona, “Neuropathology of sporadic Parkinson disease before the appearance of parkinsonism: preclinical Parkinson disease,” Journal of Neural Transmission, vol. 118, no. 5, pp. 821–839, 2011. View at Publisher · View at Google Scholar · View at Scopus
  122. G. Konopka, “Functional genomics of the brain: uncovering networks in the CNS using a systems approach,” Wiley Interdisciplinary Reviews: Systems Biology and Medicine, vol. 3, no. 6, pp. 628–648, 2011. View at Publisher · View at Google Scholar · View at Scopus