medigraphic.com
Instituto Nacional de Neurología y Neurocirugía

2015, Number 1

<< Back Next >>

Arch Neurocien 2015; 20 (1)

Molecular advances in Down syndrome and their possible application in neurology

Ramos-Kuri M, Salgado-Sánchez E

Language: Spanish
References: 66
Page: 65-78
PDF size: 369.76 Kb.


ABSTRACT

This review examines recent advances in knowledge about Down’s Syndrome (DS), with emphasis on molecular therapy and its potential in the treatment of other disorders related with DS such as Alzheimer’s Disease (AD) and cognitive impairment. The close relationship between DS and early onset AD is well-known. DS, for which there is no specific treatment yet, is the main cause of mental disability worldwide and is caused by full or partial trisomy of chromosome 21. Over-expression of genes located in this chromosome is the main cause of DS, some of them are critical for the disease. For example, DYRK1A, a dual-specificity tyrosine phosphorylation-regulated kinase, has been strongly correlated with learning impairment associated with DS and the early onset AD. The pathogenesis of DYRK1A is by hyperphosprorylation of the amyloid precursor protein (APP) and the tubulin associated unit (Tau) directly related with the AD in non SD patients. Another potential application is that DS patients have a low risk of developing solid tumors, due to suppression of angiogenesis resulting from inhibition of the vascular endothelial growth factor (VEGF) via the inhibition of calcineurin pathway by DSCR-1 protein, that is over-expressed in the 21st chromosome. Molecular therapy for DS using two vasoactive intestinal peptides (NAP and SAL) is still at experimental level and has been tried only in murine models, but has shown considerable potential in the treatment of developmental delay and learning deficits in DS and other neurological disease.


REFERENCES

  1. Mégarbané A, Ravel A, Mircher C, Sturtz F, Grattau Y, Rethoré MO, et al. The 50th anniversary of the discovery of trisomy 21: The past, present, and future of research and treatment of Down syndrome. Genet Med 2009;11(9):611-6.

  2. National Down SyndromeSociety. ¿Qué es el síndrome de Down? 2012. http://www.ndss.org/Resources/NDSS-en-Espanol/ Sobre-de-Sindrome-de-Down/Que-es-el-Sindrome-de-Down/ #sthash.3YdeERJV.dpuf

  3. Lejeune J, Gauthier M, Turpin R. Les chromosomes humains en culture de tissus. C R Hebd Seances Acad Sci 1959; 248(4):602-3.

  4. Lejeune J, Gauthier M, Turpin R. Etude des chromosomes somatiques de neuf enfants mongoliens. C R Hebd Seances Acad Sci 1959;248(11):1721-2.

  5. Hassold T, Abruzzo M, Adkins K, Griffin D, Merrill M, Millie E, et al. Human aneuploidy: Incidence, origin, and etiology. Environ Mol Mutagen 1996;28:167-75.

  6. Parker S E, Mai C T, Canfield M A, Rickard R, Wang Y, Meyer R E, et al. Updated National birth prevalence estimates for selected birth defects in the United States 2004-2006. Birth Defects Res A Clin Mol Teratol 2010;88:1008-16.

  7. Graves-Allen E, Freeman S B, Druschel C, Hobbs CA, O’Leary L A, Romitti P A, et al. Maternal age and risk for trisomy 21 assessed by the origin of chromosome nondisjunction: A report from the Atlanta and National Down Syndrome Projects. Hum Genet 2009; 125(1):41-52.

  8. Vranekoviæ J, Bo•ovic I B, Grubic Z, Wagner J, Pavliniæ D, Dahoun S, et al. Down syndrome: parental origin, recombination, and maternal age. Genentic Testing and Molecular Biomarkers 2012;16(1):70-3.

  9. Ghosh S, Feingold E, kumar Dey S. Etiology of Down syndrome: Evidence for consistent association among altered meiotic recombination, nondisjunction and maternal age across populations. Am J Med Genet A 2009; 149A(7):1415-20.

  10. Morris J K, Wald N J, Watt H C. Fetal loss in Down syndrome pregnancies. Prenat Diagn 1999; 19:142-5.

  11. Li LB, Chang KH, Wang PR, Hitara RK, Papayannopoulou T, Rusell D W. Trisomy correction in Down syndrome induced pluripotent stem cell. Cell Stem Cell 2012; 11(5):615-9.

  12. Guizar-Vázquez JJ. Genética clínica. Diagnóstico y manejo de enfermedades hereditarias. 3ª Edición. México, DF. Editorial el Manual Moderno, S.A. de C.V. 2001:127-8.

  13. Weijerman M E, De Winter J P. The care of children with Down syndrome. Eur J Pediatr 2010;169:1445-52.

  14. Wegiel J, Gong C, Hwan Y. The role of DYRK1A in neurodegenerative disease. Febs J 2011; 278(2):236-45.

  15. Warren B, Zigman, Darlynne A, Devenny, Sharon J, Krinsky- McHale, et al.Alzheimer’s disease in adults with Down syndrome. Int Rev Res Ment Retard 2008; 1(36):103-45.

  16. Vis J C, Duffels M G J, Winter M M, Weijerman M E, Cobben J M, Huisman S A, et al. Down syndrome: A cardiovascular perspective. J Intellect Disabil Res 2009; 53:419-25.

  17. Weijerman ME, van Furth AM, Vonk-Noordegraaf A, van Wouwe JP, Broers CJ, Gemke RJ. Prevalence, neonatal characteristics and first-year mortality of Down syndrome: A national study. J Pediatrics 2008; 152:15-9.

  18. Khan I, Malinge S, Crispino J D. Myeloid leukemia in Down syndrome. Crit Rev Oncog 2011; 16:25-36.

  19. Alford K A, Reinhardt K, Garnett C, Norton A, Böhmer K, Von Neuhoff C, et al. Analysis of GATA1 mutations in Down syndrome transient myeloproliferative disorder and myeloid leukemia. Blood 2011; 118:2222-38.

  20. Klusmann J, Godinho F J, Heitmann K, Maroz A, Koch M L, Reinhardt D, et al. Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakar yopoiesis and leukemogenesis. Genes & Development 2010; 24:1659-72.

  21. Xavier AC, Ge Y, Taub JW. Down Syndrome and malignancies: A unique clinical relationship. Journal of Molecular Diagnostics 2009; 11(5):371-80.

  22. Toyoda A, Noguchi H, Taylor TD, Ito T, Pletcher MT, Sakaki Y, et al. Comparative genomic sequence analysis of the human chromosome 21 Down syndrome critical region. Genome Research 2002; 12:1323-32.

  23. Nikolaev S I, Deutsch S, Genolet R, Borel C, Parand L, Ucla C, et al. Trancriptional and post-transcriptional profile of human chromosome 21. Genome Research 2009; 19:1471-9.

  24. Sommer CA, Henrique-Silva F. Trisomy 21 and Down syndrome – a short review. Braz J Biol 2008; 68(2):447-52.

  25. Wiseman F K, Alford K A, Tybulewicz VLJ, Fisher EMC. Down syndrome – recent progress and future prospects. Human Molecular Genetics 2009; 18:R75-R83.

  26. Canzonetta C, Mulligan C, Deutsch S, Ruf S, O’Doherty A, Lyle R, et al. DYRKA1-dosage imbalance perturbs NRSF/REST levels, deregulating pluripotency and embryonic stem cell fate in Down syndrome. The American Juornal of Human Genetics 2008; 83:388-400.

  27. Rueda N, Flórez J, Martínez-Cué C. Mouse models of Down syndrome as a tool to unravel the causes of mental disabilities. Neural Plasticity 2012; 2012:1-26.

  28. Vacano G N, Duval N, Patterson D. The use of mouse models for understanding the biology of Down syndrome and aging. Current Gerontology and Geriatrics Research 2012; 2012:1- 20.

  29. Asociación Down Araba - Isabel Orbe/DOWNberri. Historia del síndrome de Down.http://downberri.org/recursos/ historia-del-sindrome-de-down/

  30. Cammarata-Scalisi F, Da Silva G, Cammarata-Scalisi G, Sifuentes-C A. Historia del síndrome de Down. Un recuento lleno de protagonistas. Can Pediatr 2010; 34(3):157-159.

  31. PulevaSalud. Síndrome de Down: Historia y epidemiología. h t t p : / / w w w . p u l e v a s a l u d . c o m / p s / contenido.jsp?ID=4028&TIPO_CONTENIDO=Articulo&ID_ CATEGORIA=104863&ABRIR_SECCION=747&RUTA=1-747- 1159-104863

  32. Alberts B, Johnson A, Lewis J, et al: Molecular Biology of the Cell. 4th edition. New York: Garland Science. 2002. http:// www.ncbi.nlm.nih.gov/books/NBK26840/

  33. Hattori M, Fujiyama A, Taylor T D, Watanabe H, Yada T, Park H S, et al. The DNA sequence of human chromosome 21. Nature. 2000; 405:311-319.

  34. Shapiro B L: The Down syndrome critical region. J Neural Transm Suppl 1999; 57:41-60.

  35. Park J, Chung K C. New perspectives of Dyrk1A role in neurogenesis and neuropathologic features of Down syndrome. Exp Neurobiol 2013; 22(4):244-8.

  36. Smith B, Medda F, Gokhale V, Dunckley T, Hulme C. Recent advances in the design, synthesis, and biological evaluation of selective DYRK1A inhibitors: A new avenue for a disease modifying treatment of Alzheimer’s?. ACS Chem Neurosci 2012; 3:857"872.

  37. Tell V, Hilgeroth A. Recent developments of protein kinase Inhibitors as potential AD therapeutics. Frontiers of Cellular Neuroscience 2013; 7(Art. 189):1-8.

  38. Lott I T. Neurological phenotypes for Down syndrome across the life span. Prog Brain Res 2012; 197:101-21.

  39. Ahmed M, Dhanasekaran AR, Tong S, Wiseman F K, Fisher E M C, Tybulewicz VLJ, et al. Protein profiles in Tc1 mice implicate novel pathway perturbations in the Down syndrome brain. Human Molecular Genetics 2013; 22(9):1709-24.

  40. Wegiel J, Dowjat K, Kaczmarski W, Kuchna I, Nowicki K, Frackowiak J et al. The role of overexpressed DYRK1A protein in the early onset of neurofibrillary degeneration in Down syndrome. Acta Neuropathol 2008; 116(4): 391-407.

  41. Dressler A, Perelli V, Bozza M, Bargagna S. The autistic phenotype in Down syndrome: Differences in adaptative behavior versus Down syndrome alone and autistic disorder alone. Functional Neurology 2011; 26(3):151-8.

  42. Pescosolido MF, Yang U, Sabbagh M, Morrow EM. Lighting a path: Genetic studies pinpoint neurodevelopmental mechanisms in autism and related disorders. Dialogues in Clinical Neuroscience 2012; 14(3):239-52.

  43. Baek K H, Zaslavsky A, Lynch R C, Britt C, Okada Y, Siarey R J, et al. Down syndrome suppression of tumor growth and the role of the calcineurin inhibitor DSCR1. Nature 2009; 25,459(7250):1126-30.

  44. Lott I T. Neurological phenotypes for Down syndrome across the life span. Prog Brain Res 2012; 197:101-21.

  45. Zigman WB, Devenny DA, Krinsky-McHale SJ, Jenkins EC, Urv TK, Wegiel J, et al. Alzheimer’s disease in adults with Down syndrome. Int Rev Res Ment Retard 2008; 1(36):103-45.

  46. Secretaría de Salud. Diagnóstico prenatal de síndrome de Down. México. 2011.www.cenetec.salud.gob.mx/interior/gpc.html

  47. Eunice Kennedy Shriver National Institute of Child Health and Human Development. What are common treatments for Down syndrome? 2014. https://www.nichd.nih.gov/health/topics/ down/conditioninfo/Pages/treatments.aspx

  48. Rupareliaa A, Pearnb M L, Mobleyd WC. Cognitive and pharmacological insights from the Ts65Dn mouse model of Down syndrome. Curr Opin Neurobiol 2012; 22(5):880-6.

  49. Gardiner K J. Molecular basis of pharmacotherapies for cognition in Down syndrome. Trends Pharmacol Sci 2010; 31(2):66 p1-16.

  50. Costa A C S. On the promise of pharmacotherapies targeted at cognitive and neurodegenerative components of Down Syndrome. Dev Neurosci 2011; 33:414-27.

  51. Lockrowa J, Bogera H, Bimonte-Nelsonb H, Granholma A C. Effects of long-term memantine on memory and neuropathology in Ts65Dn mice, a model for Down syndrome. Behav Brain Res 2011; 10,221(2):610-22.

  52. Toso L, Cameroni I, Roberson R, Abebe D, Bissell S, Spong C Y. Prevention of developmental delays in Down syndrome mouse model. Obstet Gynecol 2008; 112(6):1242-51.

  53. Wilkemeyer MF, Chen S, Menkari CE, Brenneman DE, Sulik K K, Charness ME. Differential effects of ethanol antagonism and neuroprotection in peptide fragment NAPVSIPQ prevention of ethanol-induced developmental toxicity. PNAS 2003; 100(14):8543-8.

  54. Incerti M, Toso L, Vink J, Roberson R, Nold C, Abebe D, Spong C Y. Prevention of learning deficit in a Down syndrome model. Obstet Gynecol 2011; 117:354-61.

  55. Incerti M, Holowitz K, Roberson R, Abebe D, Toso L, Caballero M, et al. Prenatal treatment prevents learning deficit in Down syndrome model. Plos One 2012; 7(11):1-4.

  56. Vink J, Incerti M, Toso L, Roberson R, Abebe D, Spong C Y. Prenatal NAP+SAL prevents developmental delay in a mouse model of Down syndrome through effects on N-methyl-Daspartic acid and gamma-aminobutyric acid receptors. Am J Obstet Gynecol. 2009; 200(5):524.e1–524.e4.

  57. Gozes I, Divinski I, Piltzer I. NAP and SAL: neuroprotection against the â amyloid peptide (1-42). BMC Neuroscience 2008; 9 (Suppl 3):1-5.

  58. Quraishe S, Cowan C M, Mudher A. NAP (davunetide) rescues neuronal dysfunction in a Drosophila model of tauopathy. Molecular Psychiatry 2013; 18:834-842.

  59. Asch A. Prenatal Diagnosis and Selective Abor tion. A Challenge to Practice and Policy. Chapter six. En: Alper JS, Ard C, Asch A, Beckwith J, Conrad P, Geller LN, eds. The Double-Edged Helix. Social Implications of Genetics in a Diverse Society. Baltimore and London: The Johns Hopkins University Press, 2002:123-50.

  60. Watson, J.D. 1996. President’s Essay: Genes and Politics. Annual Report Cold Springs Harbor, Citado en Asch A 2002; 1- 20.

  61. Nizar S. Impact of UNCRPD (United Nations Convention on the Rights of Persons with Disabilities) on the status of persons with disabilities. Indian Journal of Medical Ethics. 2011; 8(4):223-229.

  62. Organización de las Naciones Unidas. Convención de las Naciones Unidas sobre los Derechos de las Personas con Discapacidad. 2007.

  63. Miller P S, Levine R L. Avoiding genetic genocide: understanding good intentions and eugenics in the complex dialogue between the medical and disability communities. Genet Med 2013; 15(2):95-102.

  64. Saxton M. Opposition to Prenatal Diagnosis and Selective Abortion. En: Parens E, editor. Prenatal Testing and Disability Rights. Washington D.C.: Georgetown University Press, 2000:147-164.

  65. Skotko BG, Levine SP, and Goldstein R. Having a brother or sister with Down syndrome: Perspectives from Siblings. Am J Med Genet A 2011; 155A(10):2348-59.

  66. Skotko BG, Levine SP, and Goldstein R. Having a son or daughter with Down syndrome: perspectives from mothers and fathers. Am J Med Genet A 2011;155A(10): 2335-47.




2020     |     www.medigraphic.com