Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA95255 | ENA |
REPOSITORIES: ENA
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Project description:The amyloid precursor protein (APP), an important player in the Alzheimer’s disease, regulates neurites formation and synaptic function by mechanisms still not fully understood. Its ability to control gene expression via its intracellular domain (AICD) was proposed to mediate several of these physiological functions. Here, we tested whether putative AICD target genes could be transcriptionally modified by the absence of APP in embryonic cortex (E18) and in primary cortical neurons during maturation after 3 or 7 days in vitro. Moreover, we aimed to identified novel APP dependent target genes that could be related to particular biological functions in the context of neuronal physiology.
2018-09-01 | GSE112847 | GEO
Project description:The amyloid precursor protein (APP) plays a central role in the pathogenesis of Alzheimerâ??s disease (AD). Processing of APP by β- and γ-secretase activities results in the production of Ã?-amyloid (AÃ?), the main constituent of Alzheimer plaques, but also in the generation of the APP intracellular domain (AICD). Recently, it has been demonstrated that AICD has transactivation potential, however, the targets of AICD dependent gene regulation and hence the physiological role of AICD remain largely unknown. In this work we analysed transcriptome changes during AICD dependent gene regulation using a human neural cell culture system inducible for expression of AICD, its co-activator Fe65, or the combination of both. Induction of AICD was associated with increased expression of genes with known function in the organization and dynamics of the actin cytoskeleton as well as genes involved in the regulation of apoptosis.
2007-06-22 | E-GEOD-4097 | biostudies-arrayexpress
Project description:Amyloid precursor protein (APP) is associated with both familial and sporadic forms of Alzheimer’s disease. APP has two homologs, amyloid precursor-like protein 1 and 2 (APLP1 and APLP2), and they have functional redundancy. APP intracellular c-terminal domain (AICD), produced by sequential α- or β- and γ-secretase cleavages, is thought to control gene expression, similarly as the ICD of Notch. To investigate the role of APP family in transcriptional regulation, we examined gene expression changes in the cerebral cortex of APP/APLP1/APLP2 conditional triple knockout (cTKO) mice, in which APP family members are selectively inactivated in excitatory neurons of the postnatal forebrain. Of the 12 previously reported AICD target genes, only Nep and Npas4 mRNA levels were significantly reduced in the cerebral cortex of cTKO mice, compared to littermate controls. We further examined global transcriptional changes by RNA-seq and identified 189 and 274 differentially expressed genes in the neocortex and hippocampus, respectively, of cTKO mice relative to controls. Gene Ontology analysis indicated that these genes are involved in a variety of cellular functions, including extracellular organization, learning and memory, and ion channels. Thus, inactivation of APP family alters transcriptional profiles of the cerebral cortex and affects wide-ranging molecular pathways.
2022-01-07 | GSE181936 | GEO
Project description:The intracellular domain of amyloid precursor protein induces the dynamic change of the gene expression profile in P19 cells.
| PRJNA128295 | ENA
Project description:The amyloid precursor protein (APP) plays a central role in the pathogenesis of Alzheimer’s disease (AD). Processing of APP by β- and γ-secretase activities results in the production of ß-amyloid (Aß), the main constituent of Alzheimer plaques, but also in the generation of the APP intracellular domain (AICD). Recently, it has been demonstrated that AICD has transactivation potential, however, the targets of AICD dependent gene regulation and hence the physiological role of AICD remain largely unknown. In this work we analysed transcriptome changes during AICD dependent gene regulation using a human neural cell culture system inducible for expression of AICD, its co-activator Fe65, or the combination of both. Induction of AICD was associated with increased expression of genes with known function in the organization and dynamics of the actin cytoskeleton as well as genes involved in the regulation of apoptosis. Keywords: (Tet-Off)
2006-05-01 | GSE4097 | GEO
Project description:Gene expression changes induced by alpha-secretase cleaved amyloid precursor protein (sAPPalpha) in organotypic hippocampal slice cultures of male, postnatal day 15 mice (C57B6/SJL). Hippocampal slice cultures were treated with phosphate buffered saline (GSM26700, GSM26701, GSM26702) or 1 nM sAPPalpha (GSM26703, GSM26704, GSM26705) for 24 h. Each sample consists of total RNA isolated from 8-12 slices from 4 mice. Data were analyzed with MAS 5.0 and scaled to 2500. sAPPalpha induces the amyloid sequestration protein transthyretin, insulin-like growth factor 2, insulin-like growth factor binding protein 2, and other genes involved in protective pathways such as apoptosis inhibition, detoxification, and retinol transport. See Stein, TD, Anders, NJ, DeCarli, C, Chan, SL, Mattson, MP, and Johnson JA. Neutralization of transthyretin reverses the neuroprotective effects of secreted APP in APPSw mice resulting in tau phosphorylation and loss of hippocampal neurons: support for the amyloid hypothesis. J Neurosci. in press.
2007-10-10 | E-GEOD-1555 | biostudies-arrayexpress
Project description:Genes induced by the Notch-Intracellular domain (NICD) in mouse mature T-cells (MT) are identifed. Among the induced Notch target genes we also identify those genes, which are regulated by the histone variant H2A.Z
2018-06-21 | GSE111029 | GEO
Project description:We found that β-amyloid accumulation is modulated in HAOEC cells by overexpression or blocking of lncRNA BACE1-AS, which in turn regulates both BACE1 mRNA and protein expression. BACE1 is key-enzyme in the synthesis of β-amyloid from Amyloid Precursor Protein (APP). The transcriptomic changes mediated by 400nM β-amyloid was investigated in HAOEC cells.
2018-12-31 | GSE84620 | GEO
Project description:Nuclear localization of intracellular domain of LDL receptor-related protein 1B induced expresion data
| PRJNA445987 | ENA
Project description:In Tg2576 mice that express a mutant form of human amyloid precursor protein linked to familial AD, genes involved in extracellular matrix structures and functions are transcriptionally upregulated, and genes involved in extracellular protein secretion and localization are differentially methylated in the transgenic mice. Integrative analysis found enrichment of GO terms related to memory and synaptic functionability. Our results indicate a possibility of transcriptional modulation by DNA methylation underlying AD neuropathology.
2023-05-03 | GSE223417 | GEO