Protein Expression in Down Syndrome Brain

ISBN-13: 9783211837320 / Angielski / Twarda / 2001 / 374 str.

Gert Lubec; G. Lubec

Opis

When we worked on Down Syndrome brain in the past we have been focus ing on adult brain. This was a major step forwards as most work on Down Syndrome was carried out on fibroblasts or other tissues and, moreover, we introduced proteomics to identify and quantify brain protein expression. We considered evaluation of brain protein expression in Down Syndrome brain by and by more important than gene hunting at the nucleic acid level realiz ing the long unpredictable way from RNA to protein. The availability of fetal samples along with the proteomic appproach stimulated and reinforced studies on Down Syndrome brain. And indeed, it was found out that some observations on aberrant protein expression in adult Down Syndrome brain could not be verified in the fetal samples indi cating that neurodegeneration in adult Down Syndrome brain may have been responsible rather than trisomy 21. Using brains from the early second trimester of gestation led to the generation of a series of clues for the under standing of aberrant wiring of the brain in Down Syndrome and enabled the determination of altered key functions in early life; e. g. undetectably low drebrin was observed in Down Syndrome cortex, an integral constituent and marker for dendritic spines, main effectors of cross-talk between neurons. In addition, evaluation of the nature of the neuronal deficits in terms of neuro transmission markers could be established as well as neuronal density in fetal Down Syndrome cortex."

Spis treści

Contents Decreased alpha-endosulfine, an endogenous regulator of ATP-sensitive potassium channels, in brains from adult Down syndrome patients Developmental instability of the cerebellum and its relevance to Down syndrome Expression of the multidrug resistance P glycoprotein (Pgp) and multidrug resistance associated protein (MRP1) in Down syndrome brains Deterioration of the transcriptional, splicing and elongation machinery in brain of fetal Down Syndrome Fetal life in Down Syndrome starts with normal neuronal density but impaired dendritic spines and synaptosomal structure Antioxidant proteins in fetal brain: superoxide dismutase-1 (SOD-1) protein is not overexpressed in fetal Down syndrome Glial-neurotrophic mechanisms in Down syndrome Aberrant expression of dihydropyrimidinase related proteins-2, -3 and -4 in fetal Down Syndrome brain Decreased protein levels of complex I 30-kDa subunit in fetal Down Syndrome brains Selective upregulation of the ubiquitin-proteasome proteolytic pathway proteins, proteasome zeta chain and isopeptidase T in fetal Down syndrome Functional genomics of Down Syndrome: a multidisciplinary approach Unaltered expression of Fas (CD95/APO-1), Caspase-3, Bcl-2 and Annexins in brain of fetal Down syndrome: evidence against increased apoptosis Alteration of caspases and other apoptosis regulatory proteins in Down syndrome Expression of apoptosis related proteins: RAIDD, ZIP kinase, Bim/BOD, p21, Bax, Bcl-2 and NF-kB in brains of patients with Down syndrome Increased brain protein levels of carbonyl reductase and alcohol dehydrogenase in Down Syndrome and Alzheimer's disease Carbohydrate handling enzymes in fetal Down Syndrome brain Changes in nicotinic acetylcholine receptor subunits expression in brain of patients with Down syndrome and Alzheimer's disease Protein levels of human peroxiredoxin subtypes in brains of patients with Alzheimer's disease and Down Syndrome Effects of a single transdermal nicotine dose on cognitive performance in adults with Down syndrome The brain in Down syndrome Decreased levels of ARPP-19 and PKA in brains of Down syndrome and Alzheimer's disease Increased protein levels of heterogeneous nuclear ribonucleoprotein A2/B1 in fetal Down syndrome brains Decreased protein levels of stathmin in adult brains with Down syndrome and Alzheimer's disease Molecular neuropathology of transgenic mouse models of Down syndrome