%0 Journal Article
%T Upregulation of CRABP1 in human neuroblastoma cells overproducing the Alzheimer-typical A¦Â42 reduces their differentiation potential
%A Markus Uhrig
%A Peter Brechlin
%A Olaf Jahn
%A Yuri Knyazev
%A Annette Weninger
%A Laura Busia
%A Kamran Honarnejad
%A Markus Otto
%A Tobias Hartmann
%J BMC Medicine
%D 2008
%I BioMed Central
%R 10.1186/1741-7015-6-38
%X A combined transcriptomics/proteomics analysis was performed to measure the effects of intracellularly generated A¦Â peptides in human neuroblastoma cells. Data was validated by real-time polymerase chain reaction (real-time PCR) and a functional validation was carried out using RNA interference.Here we studied the transcriptomic and proteomic responses to increased or decreased A¦Â42 and A¦Â40 levels generated in human neuroblastoma cells. Genome-wide expression profiles (Affymetrix) and proteomic approaches were combined to analyze the cellular response to the changed A¦Â42- and A¦Â40-levels. The cells responded to this challenge with significant changes in their expression pattern. We identified several dysregulated genes and proteins, but only the cellular retinoic acid binding protein 1 (CRABP1) was up-regulated exclusively in cells expressing an increased A¦Â42/A¦Â40 ratio. This consequently reduced all-trans retinoic acid (RA)-induced differentiation, validated by CRABP1 knock down, which led to recovery of the cellular response to RA treatment and cellular sprouting under physiological RA concentrations. Importantly, this effect was specific to the AD typical increase in the A¦Â42/A¦Â40 ratio, whereas a decreased ratio did not result in up-regulation of CRABP1.We conclude that increasing the A¦Â42/A¦Â40 ratio up-regulates CRABP1, which in turn reduces the differentiation potential of the human neuroblastoma cell line SH-SY5Y, but increases cell proliferation. This work might contribute to the better understanding of AD neurogenesis, currently a controversial topic.Alzheimer's disease (AD) is a genetically heterogeneous disorder because mutations in multiple genes are involved along with non-genetic factors [1]. The risk may be determined by the effects of numerous loci, some of which may produce only minor contributions. Amyloid precursor protein (APP), presenilin1, presenilin2 and the apolipoprotein E ¦Å4 allele have been associated with AD [2,3]. These genes are assum
%U http://www.biomedcentral.com/1741-7015/6/38