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

Weitzdoerfer, Rachel, Toran, Nuria, Subramaniyan, Saraswathi, Pollak, Arnold, Dierssen, Mara, Lubec, Gert
Amino acids 2015 v.47 no.6 pp. 1127-1134
Down syndrome, Western blotting, antibodies, biochemical pathways, brain, cognition, cortex, databases, memory, protein kinases, proteins, transforming growth factors, trisomics
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.