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Vol. 12. Issue 3.
Pages 34-40 (November 2008)
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Vol. 12. Issue 3.
Pages 34-40 (November 2008)
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El envejecimiento en el síndrome de Down: Dyrk1A como gen candidato para el declive cognitivo
Ageing in Down Syndrome: DYRK1A As a Candidate Gene for Cognitive Decline
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María Martínez de Lagrán1,2,
Corresponding author
mara.dierssen@crg.es

Correspondencia.
, Analía Bortolozzi3, Juan Gispert4, Olga Millán4, Francesc Artigas3, Cristina Fillat1,2, Maria del Mar Dierssen1,2
1 Programa Genes y Enfermedad, Centro de Regulación Genómica, (CRGUPF) PRBB, Barcelona, España
2 Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER), Barcelona, España
3 Departamento de Neuroquímica, Institut d’Investigacions Biomèdiques de Barcelona (CSIC), IDIBAPS, Barcelona, España
4 Departamento de Imagen Animal, Institut d’Alta Tecnologia (IAT-CRC Corporació Sanitària), PRBB, Barcelona, España
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Resumen

Hemos centrado esta revisión en el trabajo realizado con el objetivo de determinar el papel del gen DYRK1A en el proceso degenerativo presente en el síndrome de Down (SD), y sus mecanismos patogenéticos, utilizando como aproximación experimental modelos de ratón genéticamente modificados con diferente dosis de este gen. En base a estos resultados, proponemos que Dyrk1A es un gen dosis-sensible que, por su patrón de expresión y por los sustratos de fosforilación identificados, podría participar en las alteraciones motoras, cognitivas y el proceso neuropatológico tipo enfermedad de Alzheimer en personas con SD.

Palabras clave:
Aneuploidía
Genes dosis sensibles
Alteraciones motoras
Sistema dopaminérgico
Abstract

The DYRK1A gene has been implicated in the degenerative process observed in Down syndrome; however, its precise role and pathogenetic mechanisms are still unclear. This paper reviews experimental work conducted in genetically modified mice with differing doses of the gene. The results suggest that DYRK1A is a dosesensitive gene that may participate in motor and cognitive disturbances and in Alzheimer-like neuropathologic processes in persons with Down syndrome, according to the gene's expression pattern and the phosphorylation substrates identified.

Keywords:
Aneuploidy
Dose-sensitive genes
Motor skills disorders
Dopaminergic system
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Trabajo galardonado con el 2° Premio Ramon Trias Fargas de Investigación sobre el síndrome de Down.

Copyright © 2008. FCSD. All rights reserved
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