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A cluster of protein kinases and phosphatases modulated in fetal Down syndrome (trisomy 21) brain

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Abstract

Down syndrome (DS; trisomy 21) is the most frequent cause of mental retardation with major cognitive and behavioral deficits. Although a series of aberrant biochemical pathways has been reported, work on signaling proteins is limited. It was, therefore, the aim of the study to test a selection of protein kinases and phosphatases known to be essential for memory and learning mechanisms in fetal DS brain. 12 frontal cortices from DS brain were compared to 12 frontal cortices from controls obtained at legal abortions. Proteins were extracted from brains and western blotting with specific antibodies was carried out. Primary results were used for networking (IntAct Molecular Interaction Database) and individual predicted pathway components were subsequently quantified by western blotting. Levels of calcium–calmodulin kinase II alpha, transforming growth factor beta-activated kinase 1 as well as phosphatase and tensin homolog (PTEN) were reduced in cortex of DS subjects and network generation pointed to interaction between PTEN and the dendritic spine protein drebrin that was subsequently determined and reduced levels were observed. The findings of reduced levels of cognitive-function-related protein kinases and the phosphatase may be relevant for interpretation of previous work and may be useful for the design of future studies on signaling in DS brain. Moreover, decreased drebrin levels may point to dendritic spine abnormalities.

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The authors declare that they have no conflict of interest.

Ethical approval and informed consent

All procedures performed in studies involving human samples were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All samples were obtained by THE CIBERER BIOBANK (CBK), which is a public, non-profit-making biobank that was set up by the Biomedical Network Research Centre for Rare Diseases (CIBERER), located at the Centro de Investigación en Salud Pública (CSISP). Ethics Committee. This committee has the task of guaranteeing compliance with the ethical principles applicable to biomedical research projects incorporating human origin samples of the CBK, as well as the use made of these. CBK is attached to the Ethics Committee of the CSISP.

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Authors and Affiliations

  1. Department of Pediatrics, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria

    Rachel Weitzdoerfer, Saraswathi Subramaniyan, Arnold Pollak & Gert Lubec

  2. Department of Pathology, Hospital Universitari Vall d’Hebron, Barcelona, Spain

    Nuria Toran

  3. Genes and Disease Program, Center for Genomic Regulation and CIBERER, Barcelona, Spain

    Mara Dierssen

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  1. Rachel Weitzdoerfer
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  2. Nuria Toran
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  3. Saraswathi Subramaniyan
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  4. Arnold Pollak
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  5. Mara Dierssen
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  6. Gert Lubec
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Correspondence to Gert Lubec.

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Handling Editor: G. Lubec.

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Weitzdoerfer, R., Toran, N., Subramaniyan, S. et al. A cluster of protein kinases and phosphatases modulated in fetal Down syndrome (trisomy 21) brain. Amino Acids 47, 1127–1134 (2015). https://doi.org/10.1007/s00726-015-1941-1

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  • DOI: https://doi.org/10.1007/s00726-015-1941-1

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