New Alzheimer amyloid beta responsive genes identified in human neuroblastoma cells by hierarchical clustering.
Alzheimer's disease (AD) is characterized by neuronal degeneration and cell loss. Abeta(42), in contrast to Abeta(40), is thought to be the pathogenic form triggering the pathological cascade in AD. In order to unravel overall gene regulation we monitored the transcriptomic responses to increased or decreased Abeta(40) and Abeta(42) levels, generated and derived from its precursor C99 (C-terminal fragment of APP comprising 99 amino acids) in human neuroblastoma cells. We identified fourteen differentially expressed transcripts by hierarchical clustering and discussed their involvement in AD. These fourteen transcripts were grouped into two main clusters each showing distinct differential expression patterns depending on Abeta(40) and Abeta(42) levels. Among these transcripts we discovered an unexpected inverse and strong differential expression of neurogenin 2 (NEUROG2) and KIAA0125 in all examined cell clones. C99-overexpression had a similar effect on NEUROG2 and KIAA0125 expression as a decreased Abeta(42)/Abeta(40) ratio. Importantly however, an increased Abeta(42)/Abeta(40) ratio, which is typical of AD, had an inverse expression pattern of NEUROG2 and KIAA0125: An increased Abeta(42)/Abeta(40) ratio up-regulated NEUROG2, but down-regulated KIAA0125, whereas the opposite regulation pattern was observed for a decreased Abeta(42)/Abeta(40) ratio. We discuss the possibilities that the so far uncharacterized KIAA0125 might be a counter player of NEUROG2 and that KIAA0125 could be involved in neurogenesis, due to the involvement of NEUROG2 in developmental neural processes.
Uhrig
Markus
M
Center for Molecular Biology of the University of Heidelberg (ZMBH), Heidelberg, Germany.
Ittrich
Carina
C
Wiedmann
Verena
V
Knyazev
Yuri
Y
Weninger
Annette
A
Riemenschneider
Matthias
M
Hartmann
Tobias
T
D016229:Amyloid beta-Peptides / Q000235:genetics*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics; D009447:Neuroblastoma / Q000235:genetics / Q000473:pathology*; D016133:Polymerase Chain Reaction
D016229:Amyloid beta-Peptides; D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; C491183:NEUROG2 protein, human
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