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Acta Physiologica 2009; Volume 195, Supplement 667
XXXV Congress of The Spanish Society for Physiological Sciences
2/17/2009-2/20/2009
Valencia, Spain
THE USE OF TRANSCRIPTION FACTORS FOR CELL REPLACEMENT IN HUNTINGTONS DISEASE.
Abstract number: S62
Martin-Ibanez1 R, Urban1 N, Crespo1 E, Herranz1 C, Alberch1 J, Canals1 JM
1Departament de Biologia Cellular, Immunologia i Neurocincies, Facultat de Medicina, IDIBAPS, Universitat de Barcelona, Barcelona; Centro de Investigacin Biomdica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), SPAIN
Neurodegenerative's diseases are characterized by cell death of selective populations. The main problem for the treatment of these disorders is that when the symptoms appear a high percentage of neurons are already affected. For this reason, cell replacement strategies have been proposed. Our group is interested in to develop cell replacement strategies for Huntington's disease, a devastating disorder characterized by the degeneration of the striatal projection neurons. We have recently demonstrated that the Ikaros-family of transcription factors have a high potential to achieve our goal. Ikaros is expressed during development in the mantle zone of the lateral ganglionic eminence, the striatal primordium, where it induces cell cycle arrest of late progenitors. Ikaros-1 controls this mechanism by increasing the levels of the CDK inhibitor p21Cip/Waf1. Moreover, we showed that Ikaros-1-mediated cell cycle arrest is critical for the second wave of striatal neurogenesis that gives rise to ENK-positive neurons, the most affected in Huntington's disease. In addition, over-expression of Ikaros-1 in primary striatal cultures produces an increase in the number of calbindine and ENK-positive neurons. Similarly, Helios, another member of the Ikaros-family is also expressed in the striatum during development. Helios also participates in neurogenesis and over-expression of Helios in neural stem cells induces neuronal differentiation.
Taken together, our results indicate that Ikaros-family of transcription factors are involved in striatal development and may constitute an interesting tool to differentiate neural stem cells for cell replacement strategies.
To cite this abstract, please use the following information:
Acta Physiologica 2009; Volume 195, Supplement 667 :S62