Table of Contents Author Guidelines Submit a Manuscript
Current Gerontology and Geriatrics Research
Volume 2012, Article ID 724904, 10 pages
http://dx.doi.org/10.1155/2012/724904
Review Article

Oxidative Stress and Down Syndrome: A Route toward Alzheimer-Like Dementia

1Department of Biochemical Sciences, Faculty of Pharmacy and Medicine, Sapienza University of Rome 00185 Rome, Italy
2Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA
3Center of Membrane Sciences, University of Kentucky, Lexington, KY 40506, USA
4Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506, USA

Received 29 July 2011; Revised 10 October 2011; Accepted 11 October 2011

Academic Editor: David Patterson

Copyright © 2012 Marzia Perluigi and D. Allan Butterfield. 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. M. Dierssen, Y. Herault, and X. Estivill, “Aneuploidy: from a physiological mechanism of variance to Down syndrome,” Physiological Reviews, vol. 89, no. 3, pp. 887–920, 2009. View at Publisher · View at Google Scholar · View at Scopus
  2. D. Patterson, “Molecular genetic analysis of Down syndrome,” Human Genetics, vol. 126, no. 1, pp. 195–214, 2009. View at Publisher · View at Google Scholar · View at Scopus
  3. I. Das and R. H. Reeves, “The use of mouse models to understand and improve cognitive deficits in down syndrome,” DMM Disease Models and Mechanisms, vol. 4, no. 5, pp. 596–606, 2011. View at Publisher · View at Google Scholar
  4. R. C. Iannello, P. J. Crack, J. B. De Haan, and I. Kola, “Oxidative stress and neural dysfunction in Down syndrome,” Journal of Neural Transmission, Supplement, no. 57, pp. 257–267, 1999. View at Google Scholar · View at Scopus
  5. D. Patterson and A. C. S. Costa, “Down syndrome and genetics—a case of linked histories,” Nature Reviews Genetics, vol. 6, no. 2, pp. 137–147, 2005. View at Publisher · View at Google Scholar · View at Scopus
  6. A. Roy, I. Roberts, A. Norton, and P. Vyas, “Acute megakaryoblastic leukaemia (AMKL) and transient myeloproliferative disorder (TMD) in Down syndrome: a multi-step model of myeloid leukaemogenesis,” British Journal of Haematology, vol. 147, no. 1, pp. 3–12, 2009. View at Publisher · View at Google Scholar · View at Scopus
  7. N. J. Roizen and D. Patterson, “Down's syndrome,” The Lancet, vol. 361, no. 9365, pp. 1281–1289, 2003. View at Publisher · View at Google Scholar · View at Scopus
  8. A. H. Bittles and E. J. Glasson, “Clinical, social, and ethical implications of changing life expectancy in Down syndrome,” Developmental Medicine and Child Neurology, vol. 46, no. 4, pp. 282–286, 2004. View at Google Scholar · View at Scopus
  9. A. Bush and N. Beail, “Risk factors for dementia in people with down syndrome: issues in assessment and diagnosis,” American Journal on Mental Retardation, vol. 109, no. 2, pp. 83–97, 2004. View at Publisher · View at Google Scholar · View at Scopus
  10. M. Zana, Z. Janka, and J. Kálmán, “Oxidative stress: a bridge between Down's syndrome and Alzheimer's disease,” Neurobiology of Aging, vol. 28, no. 5, pp. 648–676, 2007. View at Publisher · View at Google Scholar · View at Scopus
  11. G. T. Capone, “Down syndrome: advances in molecular biology and the neurosciences,” Journal of Developmental and Behavioral Pediatrics, vol. 22, no. 1, pp. 40–59, 2001. View at Google Scholar · View at Scopus
  12. J. S. Krasuski, G. E. Alexander, B. Horwitz, S. I. Rapoport, and M. B. Schapiro, “Relation of medial temporal lobe volumes to age and memory function in nondemented adults with Down's syndrome: implications for the prodromal phase of Alzheimer's disease,” American Journal of Psychiatry, vol. 159, no. 1, pp. 74–81, 2002. View at Publisher · View at Google Scholar · View at Scopus
  13. A. Conti, F. Fabbrini, P. D'Agostino et al., “Altered expression of mitochondrial and extracellular matrix genes in the heart of human fetuses with chromosome 21 trisomy,” BMC Genomics, vol. 8, article 268, 2007. View at Publisher · View at Google Scholar · View at Scopus
  14. J. Busciglio and B. A. Yankner, “Apoptosis and increased generation of reactive oxygen species in Down's syndrome neurons in vitro,” Nature, vol. 378, no. 6559, pp. 776–779, 1995. View at Publisher · View at Google Scholar · View at Scopus
  15. S. V. Jovanovic, D. Clements, and K. MacLeod, “Biomarkers of oxidative stress are significantly elevated in Down syndrome,” Free Radical Biology and Medicine, vol. 25, no. 9, pp. 1044–1048, 1998. View at Publisher · View at Google Scholar · View at Scopus
  16. F. V. Pallardó, P. Degan, M. d'ischia et al., “Multiple evidence for an early age pro-oxidant state in Down Syndrome patients,” Biogerontology, vol. 7, no. 4, pp. 211–220, 2006. View at Publisher · View at Google Scholar · View at Scopus
  17. G. Cenini, A. L. Dowling, T. L. Beckett et al., “Association between frontal cortex oxidative damage and beta-amyloid as a function of age in Down Syndrome,” Biochimica et Biophysica Acta. In press.
  18. A. Nunomura, G. Perry, G. Aliev et al., “Oxidative damage is the earliest event in Alzheimer disease,” Journal of Neuropathology and Experimental Neurology, vol. 60, no. 8, pp. 759–767, 2001. View at Google Scholar · View at Scopus
  19. K. S. Rao, “Mechanisms of disease: DNA repair defects and neurological disease,” Nature Clinical Practice Neurology, vol. 3, no. 3, pp. 162–172, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. G. Benzi and A. Moretti, “Are reactive oxygen species involved in Alzheimer's disease?” Neurobiology of Aging, vol. 16, no. 4, pp. 661–674, 1995. View at Publisher · View at Google Scholar · View at Scopus
  21. J. B. de Haan, F. Cristiano, R. C. Iannello, and I. Kola, “Cu/Zn-superoxide dismutase and glutathione peroxidase during aging,” Biochemistry and Molecular Biology International, vol. 35, no. 6, pp. 1281–1297, 1995. View at Google Scholar · View at Scopus
  22. M. F. Sánchez-Font, J. Sebastià, C. Sanfeliu, R. Cristòfol, G. Marfany, and R. Gonzàlez-Duarte, “Peroxiredoxin 2 (PRDX2), an antioxidant enzyme, is under-expressed in Down syndrome fetal brains,” Cellular and Molecular Life Sciences, vol. 60, no. 7, pp. 1513–1523, 2003. View at Publisher · View at Google Scholar · View at Scopus
  23. J. H. Shin, J. London, M. Le Pecheur, H. Höger, D. Pollak, and G. Lubec, “Aberrant neuronal and mitochondrial proteins in hippocampus of transgenic mice overexpressing human Cu/Zn superoxide dismutase 1,” Free Radical Biology and Medicine, vol. 37, no. 5, pp. 643–653, 2004. View at Publisher · View at Google Scholar · View at Scopus
  24. T. Gulesserian, E. Engidawork, M. Fountoulakis, and G. Lubec, “Antioxidant proteins in fetal brain: superoxide dismutase-1 (SOD-1) protein is not overexpressed in fetal Down syndrome,” Journal of Neural Transmission, Supplement, no. 61, pp. 71–84, 2001. View at Google Scholar · View at Scopus
  25. D. Praticò, L. Iuliano, G. Amerio et al., “Down's syndrome is associated with increased 8,12-iso-iPF(2α)-VI levels: evidence for enhanced lipid peroxidation in vivo,” Annals of Neurology, vol. 48, no. 5, pp. 795–798, 2000. View at Google Scholar · View at Scopus
  26. C. Campos, R. Guzmán, E. López-Fernández, and A. Casado, “Evaluation of urinary biomarkers of oxidative/nitrosative stress in adolescents and adults with Down syndrome,” Biochimica et Biophysica Acta, vol. 1812, no. 7, pp. 760–768, 2011. View at Publisher · View at Google Scholar
  27. K. Ishihara, K. Amano, E. Takaki et al., “Increased lipid peroxidation in Down's syndrome mouse models,” Journal of Neurochemistry, vol. 110, no. 6, pp. 1965–1976, 2009. View at Publisher · View at Google Scholar · View at Scopus
  28. D. A. Butterfield, J. Drake, C. Pocernich, and A. Castegna, “Evidence of oxidative damage in Alzheimer's disease brain: central role for amyloid β-peptide,” Trends in Molecular Medicine, vol. 7, no. 12, pp. 548–554, 2001. View at Publisher · View at Google Scholar · View at Scopus
  29. D. A. Butterfield and C. M. Lauderback, “Lipid peroxidation and protein oxidation in Alzheimer's disease brain: potential causes and consequences involving amyloid β-peptide-associated free radical oxidative stress,” Free Radical Biology and Medicine, vol. 32, no. 11, pp. 1050–1060, 2002. View at Publisher · View at Google Scholar · View at Scopus
  30. D. A. Butterfield, V. Galvan, M. B. Lange et al., “In vivo oxidative stress in brain of Alzheimer disease transgenic mice: requirement for methionine 35 in amyloid β-peptide of APP,” Free Radical Biology and Medicine, vol. 48, no. 1, pp. 136–144, 2010. View at Publisher · View at Google Scholar · View at Scopus
  31. B. Mazur-Kolecka, A. Golabek, K. Nowicki, M. Flory, and J. Frackowiak, “Amyloid-β impairs development of neuronal progenitor cells by oxidative mechanisms,” Neurobiology of Aging, vol. 27, no. 9, pp. 1181–1192, 2006. View at Publisher · View at Google Scholar · View at Scopus
  32. E. Head and I. T. Lott, “Down syndrome and beta-amyloid deposition,” Current Opinion in Neurology, vol. 17, no. 2, pp. 95–100, 2004. View at Publisher · View at Google Scholar · View at Scopus
  33. P. D. Mehta, G. Capone, A. Jewell, and R. L. Freedland, “Increased amyloid β protein levels in children and adolescents with Down syndrome,” Journal of the Neurological Sciences, vol. 254, no. 1-2, pp. 22–27, 2007. View at Publisher · View at Google Scholar · View at Scopus
  34. N. Schupf, W. B. Zigman, M. X. Tang et al., “Change in plasma Aβ peptides and onset of dementia in adults with Down syndrome,” Neurology, vol. 75, no. 18, pp. 1639–1644, 2010. View at Publisher · View at Google Scholar · View at Scopus
  35. H. K. Anandatheerthavarada, G. Biswas, M. A. Robin, and N. G. Avadhani, “Mitochondrial targeting and a novel transmembrane arrest of Alzheimer's amyloid precursor protein impairs mitochondrial function in neuronal cells,” Journal of Cell Biology, vol. 161, no. 1, pp. 41–54, 2003. View at Publisher · View at Google Scholar · View at Scopus
  36. A.-M. Simón, L. Schiapparelli, P. Salazar-Colocho et al., “Overexpression of wild-type human APP in mice causes cognitive deficits and pathological features unrelated to Aβ levels,” Neurobiology of Disease, vol. 33, no. 3, pp. 369–378, 2009. View at Publisher · View at Google Scholar
  37. G. Azkona, D. Levannon, Y. Groner, and M. Dierssen, “In vivo effects of APP are not exacerbated by BACE2 co-overexpression: behavioural characterization of a double transgenic mouse model,” Amino Acids, vol. 39, no. 5, pp. 1571–1580, 2010. View at Publisher · View at Google Scholar · View at Scopus
  38. B. Balcz, L. Kirchner, N. Cairns, M. Fountoulakis, and G. Lubec, “Increased brain protein levels of carbonyl reductase and alcohol dehydrogenase in Down Syndrome and Alzheimer's disease,” Journal of Neural Transmission, Supplement, no. 61, pp. 193–201, 2001. View at Google Scholar · View at Scopus
  39. T. Reed, M. Perluigi, R. Sultana et al., “Redox proteomic identification of 4-Hydroxy-2-nonenal-modified brain proteins in amnestic mild cognitive impairment: insight into the role of lipid peroxidation in the progression and pathogenesis of Alzheimer's disease,” Neurobiology of Disease, vol. 30, no. 1, pp. 107–120, 2008. View at Publisher · View at Google Scholar · View at Scopus
  40. M. Munke, J. P. Kraus, T. Ohura, and U. Francke, “The gene for cystathionine β-synthase (CBS) maps to the subtelomeric region on human chromosome 21q and to proximal mouse chromosome 17,” American Journal of Human Genetics, vol. 42, no. 4, pp. 550–559, 1988. View at Google Scholar · View at Scopus
  41. K. Hensley, K. Venkova, and A. Christov, “Emerging biological importance of central nervous system lanthionines,” Molecules, vol. 15, no. 8, pp. 5581–5594, 2010. View at Publisher · View at Google Scholar · View at Scopus
  42. K. Eto, T. Asada, K. Arima, T. Makifuchi, and H. Kimura, “Brain hydrogen sulfide is severely decreased in Alzheimer's disease,” Biochemical and Biophysical Research Communications, vol. 293, no. 5, pp. 1485–1488, 2002. View at Publisher · View at Google Scholar · View at Scopus
  43. A. Ichinohe, T. Kanaumi, S. Takashima, Y. Enokido, Y. Nagai, and H. Kimura, “Cystathionine β-synthase is enriched in the brains of Down's patients,” Biochemical and Biophysical Research Communications, vol. 338, no. 3, pp. 1547–1550, 2005. View at Publisher · View at Google Scholar
  44. P. Kamoun, M. C. Belardinelli, A. Chabli, K. Lallouchi, and B. Chadefaux-Vekemans, “Endogenous hydrogen sulfide overproduction in Down syndrome,” American Journal of Medical Genetics, vol. 116, no. 3, pp. 310–311, 2003. View at Google Scholar · View at Scopus
  45. P. Kamoun, “Mental retardation in Down syndrome: a hydrogen sulfide hypothesis,” Medical Hypotheses, vol. 57, no. 3, pp. 389–392, 2001. View at Publisher · View at Google Scholar · View at Scopus
  46. K. Beyer, J. I. Lao, C. Carrato et al., “Cystathionine beta synthase as a risk factor for Alzheimer disease,” Curr Alzheimer Res, vol. 1, no. 2, pp. 127–133, 2004. View at Google Scholar · View at Scopus
  47. A. J. Knox, C. Graham, J. Bleskan, G. Brodsky, and D. Patterson, “Mutations in the Chinese hamster ovary cell GART gene of de novo purine synthesis,” Gene, vol. 429, no. 1-2, pp. 23–30, 2009. View at Publisher · View at Google Scholar · View at Scopus
  48. I. Zitnanova, P. Korytár, O. I. Aruoma et al., “Uric acid and allantoin levels in Down syndrome: antioxidant and oxidative stress mechanisms?” Clinica Chimica Acta, vol. 341, no. 1-2, pp. 139–146, 2004. View at Publisher · View at Google Scholar · View at Scopus
  49. G. Esposito, D. De Filippis, C. Cirillo, G. Sarnelli, R. Cuomo, and T. Iuvone, “The astroglial-derived S100β protein stimulates the expression of nitric oxide synthase in rodent macrophages through p38 MAP kinase activation,” Life Sciences, vol. 78, no. 23, pp. 2707–2715, 2006. View at Publisher · View at Google Scholar · View at Scopus
  50. M. C. Royston, J. E. McKenzie, S. M. Gentleman et al., “Overexpression of S100β in Down's syndrome: correlation with patient age and with β-amyloid deposition,” Neuropathology and Applied Neurobiology, vol. 25, no. 5, pp. 387–393, 1999. View at Publisher · View at Google Scholar
  51. P. Odetti, G. Angelini, D. Dapino et al., “Early glycoxidation damage in brains from Down's syndrome,” Biochemical and Biophysical Research Communications, vol. 243, no. 3, pp. 849–851, 1998. View at Publisher · View at Google Scholar · View at Scopus
  52. A. Nunomura, G. Perry, M. A. Pappolla et al., “Neuronal oxidative stress precedes amyloid-β deposition in down syndrome,” Journal of Neuropathology and Experimental Neurology, vol. 59, no. 11, pp. 1011–1017, 2000. View at Google Scholar · View at Scopus
  53. C. Campos, R. Guzmán, E. López-Fernández, and A. Casado, “Urinary biomarkers of oxidative/nitrosative stress in healthy smokers,” Inhalation Toxicology, vol. 23, no. 3, pp. 148–156, 2011. View at Publisher · View at Google Scholar
  54. C. Liu, P. V. Belichenko, L. Zhang et al., “Mouse models for down syndrome-associated developmental cognitive disabilities,” Developmental Neuroscience. In press.
  55. L. E. Olson, R. J. Roper, L. L. Baxter, E. J. Carlson, C. J. Epstein, and R. H. Reeves, “Down syndrome mouse models Ts65Dn, Ts1Cje, and Ms1Cje/Ts65Dn exhibit variable severity of cerebellar phenotypes,” Developmental Dynamics, vol. 230, no. 3, pp. 581–589, 2004. View at Publisher · View at Google Scholar · View at Scopus
  56. J. T. Richtsmeier, A. Zumwalt, E. J. Carlson, C. J. Epstein, and R. H. Reeves, “Craniofacial phenotypes in segmentally trisomic mouse models for Down syndrome,” American Journal of Medical Genetics, vol. 107, no. 4, pp. 317–324, 2002. View at Publisher · View at Google Scholar · View at Scopus
  57. H. Sago, E. J. Carlson, D. J. Smith et al., “Ts1Cje, a partial trisomy 16 mouse model for Down syndrome, exhibits learning and behavioral abnormalities,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 11, pp. 6256–6261, 1998. View at Publisher · View at Google Scholar · View at Scopus
  58. D. A. Butterfield, M. L. Bader Lange, and R. Sultana, “Involvements of the lipid peroxidation product, HNE, in the pathogenesis and progression of Alzheimer's disease,” Biochimica et Biophysica Acta, vol. 1801, no. 8, pp. 924–929, 2010. View at Publisher · View at Google Scholar · View at Scopus
  59. M. Perluigi, R. Sultana, G. Cenini et al., “Redox proteomics identification of 4-hydroxynonenalmodified brain proteins in Alzheimer's disease: role of lipid peroxidation in Alzheimer's disease pathogenesis,” Proteomics—Clinical Applications, vol. 3, no. 6, pp. 682–693, 2009. View at Publisher · View at Google Scholar · View at Scopus
  60. M. A. Underwood, W. M. Gilbert, and M. P. Sherman, “Amniotic fluid: not just fetal urine anymore,” Journal of Perinatology, vol. 25, no. 5, pp. 341–348, 2005. View at Publisher · View at Google Scholar · View at Scopus
  61. C. K. J. Cho, C. R. Smith, and E. P. Diamandis, “Amniotic fluid proteome analysis from down syndrome pregnancies for biomarker discovery,” Journal of Proteome Research, vol. 9, no. 7, pp. 3574–3582, 2010. View at Publisher · View at Google Scholar · View at Scopus
  62. A. Kolialexi, G. Tounta, A. Mavrou, and G. T. Tsangaris, “Proteomic analysis of amniotic fluid for the diagnosis of fetal aneuploidies,” Expert Review of Proteomics, vol. 8, no. 2, pp. 175–185, 2011. View at Publisher · View at Google Scholar
  63. M. Perluigi, F. di Domenico, A. Fiorini et al., “Oxidative stress occurs early in Down syndrome pregnancy: a redox proteomics analysis of amniotic fluid,” Proteomics—Clinical Applications, vol. 5, no. 3-4, pp. 167–178, 2011. View at Publisher · View at Google Scholar
  64. I. T. Lott, E. Head, E. Doran, and J. Busciglio, “Beta-amyloid, oxidative stress and down syndrome,” Current Alzheimer Research, vol. 3, no. 5, pp. 521–528, 2006. View at Publisher · View at Google Scholar · View at Scopus
  65. E. Head, I. T. Lott, D. Patterson, E. Doran, and R. J. Haier, “Possible compensatory events in adult Down syndrome brain prior to the development of Alzheimer disease neuropathology: targets for nonpharmacological intervention,” Journal of Alzheimer's Disease, vol. 11, no. 1, pp. 61–76, 2007. View at Google Scholar · View at Scopus
  66. E. Head, E. Doran, M. Nistor et al., “Plasma amyloid-β as a function of age, level of intellectual disability, and presence of dementia in down syndrome,” Journal of Alzheimer's Disease, vol. 23, no. 3, pp. 399–409, 2011. View at Publisher · View at Google Scholar
  67. M. Nistor, M. Don, M. Parekh et al., “Alpha- and beta-secretase activity as a function of age and beta-amyloid in Down syndrome and normal brain,” Neurobiology of Aging, vol. 28, no. 10, pp. 1493–1506, 2007. View at Publisher · View at Google Scholar · View at Scopus
  68. E. Head, B. Y. Azizeh, I. T. Lott, A. J. Tenner, C. W. Cotman, and D. H. Cribbs, “Complement association with neurons and β-amyloid deposition in the brains of aged individuals with Down Syndrome,” Neurobiology of Disease, vol. 8, no. 2, pp. 252–265, 2001. View at Publisher · View at Google Scholar · View at Scopus
  69. A. M. Cataldo, S. Petanceska, C. M. Peterhoff et al., “App gene dosage modulates endosomal abnormalities of Alzheimer's disease in a segmental trisomy 16 mouse model of Down syndrome,” Journal of Neuroscience, vol. 23, no. 17, pp. 6788–6792, 2003. View at Google Scholar · View at Scopus
  70. I. T. Lott and E. Head, “Down syndrome and alzheimer's disease: a link between development and aging,” Mental Retardation and Developmental Disabilities Research Reviews, vol. 7, no. 3, pp. 172–178, 2001. View at Publisher · View at Google Scholar · View at Scopus
  71. J. Busciglio, A. Pelsman, C. Wong et al., “Altered metabolism of the amyloid β precursor protein is associated with mitochondrial dysfunction in Down's syndrome,” Neuron, vol. 33, no. 5, pp. 677–688, 2002. View at Publisher · View at Google Scholar · View at Scopus
  72. J. Busciglio, A. Pelsman, P. Helguera et al., “NAP and ADNF-9 protect normal and Down's syndrome cortical neurons from oxidative damage and apoptosis,” Current Pharmaceutical Design, vol. 13, no. 11, pp. 1091–1098, 2007. View at Publisher · View at Google Scholar · View at Scopus
  73. S. Perrone, M. Longini, C. V. Bellieni et al., “Early oxidative stress in amniotic fluid of pregnancies with Down syndrome,” Clinical Biochemistry, vol. 40, no. 3-4, pp. 177–180, 2007. View at Publisher · View at Google Scholar · View at Scopus
  74. M. Zana, A. Szécsényi, Á. Czibula et al., “Age-dependent oxidative stress-induced DNA damage in Down's lymphocytes,” Biochemical and Biophysical Research Communications, vol. 345, no. 2, pp. 726–733, 2006. View at Publisher · View at Google Scholar · View at Scopus
  75. M. P. Mattson, B. Cheng, A. R. Culwell, F. S. Esch, I. Lieberburg, and R. E. Rydel, “Evidence for excitoprotective and intraneuronal calcium-regulating roles for secreted forms of the β-amyloid precursor protein,” Neuron, vol. 10, no. 2, pp. 243–254, 1993. View at Publisher · View at Google Scholar · View at Scopus
  76. D. Schubert, L. W. Jin, T. Saitoh, and G. Cole, “The regulation of amyloid β protein precursor secretion and its modulatory role in cell adhesion,” Neuron, vol. 3, no. 6, pp. 689–694, 1989. View at Google Scholar · View at Scopus
  77. C. Russo, V. Venezia, E. Repetto et al., “The amyloid precursor protein and its network of interacting proteins: physiological and pathological implications,” Brain Research Reviews, vol. 48, no. 2, pp. 257–264, 2005. View at Publisher · View at Google Scholar · View at Scopus
  78. D. J. Keating, C. Chen, and M. A. Pritchard, “Alzheimer's disease and endocytic dysfunction: clues from the Down syndrome-related proteins, DSCR1 and ITSN1,” Ageing Research Reviews, vol. 5, no. 4, pp. 388–401, 2006. View at Publisher · View at Google Scholar · View at Scopus
  79. G. Ermak, C. Cheadle, K. G. Becker, C. D. Harris, and K. J. A. Davies, “DSCR1(Adapt78) modulates expression of SOD1,” The FASEB Journal, vol. 18, no. 1, pp. 62–69, 2004. View at Publisher · View at Google Scholar · View at Scopus
  80. K. T. Chang and K. T. Min, “Drosophila melanogaster homolog of Down syndrome critical region 1 is critical for mitochondrial function,” Nature Neuroscience, vol. 8, no. 11, pp. 1577–1585, 2005. View at Publisher · View at Google Scholar · View at Scopus
  81. E. T. Bersu, F. J. Ahmad, M. J. Schwei, and P. W. Baas, “Cytoplasmic abnormalities in cultured cerebellar neurons from the trisomy 16 mouse,” Developmental Brain Research, vol. 109, no. 1, pp. 115–120, 1998. View at Publisher · View at Google Scholar · View at Scopus
  82. J. Prince, S. Jia, U. Bave, G. Anneren, and L. Oreland, “Mitochondrial enzyme deficiencies in Down's syndrome,” Journal of Neural Transmission—Parkinson's Disease and Dementia Section, vol. 8, no. 3, pp. 171–181, 1994. View at Publisher · View at Google Scholar · View at Scopus
  83. N. Howell, J. L. Elson, P. F. Chinnery, and D. M. Turnbull, “mtDNA mutations and common neurodegenerative disorders,” Trends in Genetics, vol. 21, no. 11, pp. 583–586, 2005. View at Publisher · View at Google Scholar · View at Scopus
  84. S. Arbuzova, T. Hutchin, and H. Cuckle, “Mitochondrial dysfunction and Down's syndrome,” BioEssays, vol. 24, no. 8, pp. 681–684, 2002. View at Publisher · View at Google Scholar · View at Scopus
  85. P. Coskun, J. Wyrembak, S. Schriner et al., “A mitochondrial etiology of Alzheimer and Parkinson disease,” Biochimica et Biophysica Acta. In press.
  86. D. C. Wallace, “Mitochondrial diseases in man and mouse,” Science, vol. 283, no. 5407, pp. 1482–1488, 1999. View at Publisher · View at Google Scholar · View at Scopus
  87. N. Druzhyna, R. G. Nair, S. P. Ledoux, and G. L. Wilson, “Defective repair of oxidative damage in mitochondrial DNA in Down's syndrome,” Mutation Research, vol. 409, no. 2, pp. 81–89, 1998. View at Publisher · View at Google Scholar · View at Scopus
  88. S. Schuchmann and U. Heinemann, “Increased mitochondrial superoxide generation in neurons from trisomy 16 mice: a model of Down's syndrome,” Free Radical Biology and Medicine, vol. 28, no. 2, pp. 235–250, 2000. View at Publisher · View at Google Scholar · View at Scopus
  89. L. L. Bambrick and G. Fiskum, “Mitochondrial dysfunction in mouse trisomy 16 brain,” Brain Research, vol. 1188, no. 1, pp. 9–16, 2008. View at Publisher · View at Google Scholar · View at Scopus
  90. D. Valenti, G. A. Manente, L. Moro, E. Marra, and R. A. Vacca, “Deficit of complex I activity in human skin fibroblasts with chromosome 21 trisomy and overproduction of reactive oxygen species by mitochondria: involvement of the cAMP/PKA signalling pathway,” Biochemical Journal, vol. 435, no. 3, pp. 679–688, 2011. View at Publisher · View at Google Scholar
  91. H. Li and G. Dryhurst, “Oxidative metabolites of 5-S-cysteinyldopamine inhibit the pyruvate dehydrogenase complex,” Journal of Neural Transmission, vol. 108, no. 12, pp. 1363–1374, 2001. View at Publisher · View at Google Scholar · View at Scopus
  92. E. Roat, N. Prada, R. Ferraresi et al., “Mitochondrial alterations and tendency to apoptosis in peripheral blood cells from children with Down syndrome,” FEBS Letters, vol. 581, no. 3, pp. 521–525, 2007. View at Publisher · View at Google Scholar · View at Scopus
  93. V. Infantino, A. Castegna, F. Iacobazzi et al., “Impairment of methyl cycle affects mitochondrial methyl availability and glutathione level in Down's syndrome,” Molecular Genetics and Metabolism, vol. 102, no. 3, pp. 378–382, 2011. View at Publisher · View at Google Scholar
  94. I. T. Lott, E. Doran, V. Q. Nguyen, A. Tournay, E. Head, and D. L. Gillen, “Down syndrome and dementia: a randomized, controlled trial of antioxidant supplementation,” American Journal of Medical Genetics, Part A, vol. 155, no. 8, pp. 1939–1948, 2011. View at Publisher · View at Google Scholar
  95. J. Lockrow, A. Prakasam, P. Huang, H. Bimonte-Nelson, K. Sambamurti, and A. C. Granholm, “Cholinergic degeneration and memory loss delayed by vitamin E in a Down syndrome mouse model,” Experimental Neurology, vol. 216, no. 2, pp. 278–289, 2009. View at Publisher · View at Google Scholar · View at Scopus