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• Triplication of DYRK1A causes retinal structural and functional alterations in Down
Most relevant
syndrome. laGuna a, barallobre MJ, Marchena Má, Mateus c, raMírez e, Martínez-cue
scientific c, d JM, c-b M, V P, a Ml. Hum Mol Genet. 2013 Jul
elabarastelorancode la illarbonés
articles
15;22(14):2775-84. PMID: 23512985.

• Environmental enrichment rescues DYRK1A activity and hippocampal adult neuro-

genesis in TgDyrk1A. Pons-esPinal M, Martínez de laGran M, dierssen M. Neurobiol Dis.
2013 Dec;60:18-31. PMID: 23969234.

• Normalization of Dyrk1A expression by AAV2/1-shDyrk1A attenuates hippocampal-

dependent defects in the Ts65Dn mouse model of Down syndrome. altaFaJ X, Martín
ed, o-a J, V a, l-P c, d M, F c. Neurobiol Dis.
rtizbaliaalderraMaaoereGrínierssenillat
2013 Apr;52:117-27. PMID: 23220201.

• Hippocampal hyperexcitability underlies enhanced fear memories in TgNTRK3, a pa-
nic disorder mouse model. s M, d’a d, s o, a-a a, s o,
antosMicoPadoniMadorrJonatork
dierssen M. J neurosci. 2013 Sep 18;33(38):15259-71. PMID: 24048855.

• Intraductal delivery of adenoviruses targets pancreatic tumors in transgenic Ela-myc

mice and orthotopic xenografts. José a, sobreVals l, MiGuel caMacho-sánchez J, huch M,
andreu n, ayuso e, naVarro P, aleMany r, Fillat c. Oncotarget. 2013 Jan;4(1):94-105.

PMID: 23328228.

Highlights
The team focuses its research on the study of the molecular basis, the pathophy-
siological mechanisms and therapeutic approaches of neurodevelopmental genetic

diseases with a special interest on aneuploidies associated to human chromosome
21 (HSA21). Moreover, the group develops therapeutic strategies for rare tumours.

In 2013, the group contributions have shown that overexpression of the HSA21

gene DYRK1A involves neurodevelopmental alterations that contribute to pheno-
types associated with Down syndrome (DS), such are the motor phenotypes and

the cellular and electrophysiological alterations of the retina. Our results have also

shown that, in the adult, DYRK1A overexpression is linked to deleterious effects of
the cholinergic system, as well as changes in synaptic plasticity and neurogenesis

in hippocampus. Alterations in adult neurogenesis have been partially rescued by

a pharmacological inhibitor of the kinase. The pathological contribution in a triso-
mic context has been evidenced by the attenuation of the synaptic plasticity de-

fects achieved after normalization of Dyrk1A expression in trisomic mice by gene
therapy. Regarding RCAN1, another key gene in DS, the group has helped to show

that its overexpression is associated with the immune system dysfunction in DS .

We highlight two achievements of the group in 2013: 1) the development of a

clinical trial (NCT01699711 ) in collaboration with the IMIM-Hospital del Mar on
the “Use of epigallocatechin gallate in modulating Dyrk1A and APP and assess its

impact on the cognitive performance in patients with Down syndrome “ and 2) the
granting of the XIII Ramon Trias Fargas Research Award 2013 on Down syndrome 13
20
to the work “ Understanding Down syndrome with the help of viruses “ presented T
OR
by our group.
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