Reduced Levels of DEAD-Box Proteins DBP-RB and p72 in Fetal Down Syndrome Brains (original) (raw)
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ABERRANT PROTEIN EXPRESSION IN CEREBRAL CORTEX OF FETUS WITH DOWN SYNDROME
Abstract—Down syndrome is the most common birth defect associated with mental retardation. Identifying proteins that are aberrantly expressed therefore helps to understand how chromosomal imbalance leads to subnormal intelligence in Down syndrome. In the present study, we generated a fetal brain map with the use of an analytical method based on two-dimensional electrophoresis coupled with mass spectrometry and searched the proteome for differential protein expression. Among 49 proteins analyzed in seven control and nine Down syndrome fetuses, we found 11 proteins that have been deregulated in cerebral cortex of fetal Down syndrome. While double-strand break repair protein rad 21 homologue, eukaryotic translation initiation factor 3 subunit 5, mixed lineage leukemia septin-like fusion protein-B and heat shock protein 75 were increased; -amyloid precursor-like protein 1, tropomyosin 4-anaplastic lymphoma kinase fusion oncoprotein type 2, Nck adaptor protein 2, Src homology domain growth factor receptor bound 2-like endophilin B2, tubulin, septin 7 and hematopoietic stem/progenitor cells 140 were decreased. The current data suggest that misexpression of proteins that have functions ranging from signaling to cellular structural organization could contribute to or reflect brain dysgenesis in Down syndrome. © 2003 IBRO. Published by Elsevier Ltd. All rights reserved. Key words: septins, -tubulin, fusion oncoproteins, DNA repair proteins, Nck adaptor protein 2, -amyloid precursor-like protein.
Molecular changes in fetal Down syndrome brain
Trisomy of human chromosome 21 is a major cause of mental retardation and other phenotypic abnormalities collectively known as Down syndrome. Down syndrome is associated with developmental failure followed by processes of neurodegeneration that are known to supervene later in life. Despite a widespread interest in Down syndrome, the cause of developmental failure is unclear. The brain of a child with Down syndrome develops differently from that of a normal one, although characteristic morphological differences have not been noted in prenatal life. On the other hand, a review of theexisting literature indicates that there are a series of biochemical alterations occurring in fetal Down syndrome brain that could serve as substrate for morphological changes. We propose that these biochemical alterations represent and/or precede morphological changes. This review attempts to dissect these molecular changes and to explain how they may lead to mental retardation. Keywords: brain, cytoskeleton, fetal Down syndrome, mental retardation, signalling. J. Neurochem. (2003) 84, 895–904.
Journal of Neurochemistry, 2006
To understand the aetiology and the phenotypic severity of Down syndrome, we searched for transcriptional signatures in a substructure of the brain (cerebellum) during post-natal development in a segmental trisomy 16 model, the Ts1Cje mouse. The goal of this study was to investigate the effects of trisomy on changes in gene expression across development time. The primary gene-dosage effect on triplicated genes (∼1.5) was observed at birth [post-natal day 0 (P0)], at P15 and P30. About 5% of the non-triplicated genes were significantly differentially expressed between trisomic and control cerebellum, while 25% of the transcriptome was modified during post-natal development of the cerebellum. Indeed, only 165, 171 and 115 genes were dysregulated in trisomic cerebellum at P0, P15 and P30, respectively. Surprisingly, there were only three genes dysregulated in development and in trisomic animals in a similar or opposite direction. These three genes (Dscr1, Son and Hmg14) were, quite unexpectedly, triplicated in the Ts1Cje model and should be candidate genes for understanding the aetiology of the phenotype observed in the cerebellum.
Colombia Medica
The information of gene expression obtained from databases, have made possible the extraction and analysis of data related with several molecular processes involving not only in brain homeostasis but its disruption in some neuropathologies; principally in Down syndrome and the Alzheimer disease. To correlate the levels of transcription of 19 genes located in the Down Syndrome Critical Region (DSCR) with their expression in several substructures of normal human brain. There were obtained expression profiles of 19 DSCR genes in 42 brain substructures, from gene expression values available at the database of the human brain of the Brain Atlas of the Allen Institute for Brain Sciences", (http://human.brain-map.org/). The co-expression patterns of DSCR genes in brain were calculated by using multivariate statistical methods. Highest levels of gene expression were registered at caudate nucleus, nucleus accumbens and putamen among central areas of cerebral cortex. Increased expression...