Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Alzheimer's disease-related dysregulation of mRNA translation causes key pathological features with ageing

ABSTRACT: Alzheimer's disease-related dysregulation of mRNA translation causes key pathological features with ageing

PROVIDER: PRJNA642886 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Alzheimer's disease-related dysregulation of mRNA translation causes key pathological features with ageing.

Project description:Alzheimer's disease (AD) is characterised by Aβ and tau pathology as well as synaptic degeneration, which correlates best with cognitive impairment. Previous work suggested that this pathological complexity may result from changes in mRNA translation. Here, we studied whether mRNA translation and its underlying signalling are altered in an early model of AD, and whether modelling this deficiency in mice causes pathological features with ageing. Using an unbiased screen, we show that exposure of primary neurons to nanomolar amounts of Aβ increases FMRP-regulated protein synthesis. This selective regulation of mRNA translation is dependent on a signalling cascade involving MAPK-interacting kinase 1 (Mnk1) and the eukaryotic initiation factor 4E (eIF4E), and ultimately results in reduction of CYFIP2, an FMRP-binding protein. Modelling this CYFIP2 reduction in mice, we find age-dependent Aβ accumulation in the thalamus, development of tau pathology in entorhinal cortex and hippocampus, as well as gliosis and synapse loss in the hippocampus, together with deficits in memory formation. Therefore, we conclude that early stages of AD involve increased translation of specific CYFIP2/FMRP-regulated transcripts. Since reducing endogenous CYFIP2 expression is sufficient to cause key features of AD with ageing in mice, we suggest that prolonged activation of this pathway is a primary step toward AD pathology, highlighting a novel direction for therapeutic targeting.

| S-EPMC7297996 | biostudies-literature

Alzheimer's disease-related dysregulation of mRNA translation causes key pathological features with ageing

Project description:Primary rat cortical neurons and treated with AB for 24h. RNA-seq on total and ribosome-enriched sucrose cushion

2020-06-29 | GSE149540 | GEO

Microarray analysis of the astrocyte transcriptome in the ageing brain: relationship to Alzheimer's pathology and ApoE genotype

2011-06-01 | GSE29652 | GEO

Dysregulation of the epigenetic landscape of normal aging in Alzheimer's disease

Project description:Dysregulation of the epigenetic landscape of normal aging in Alzheimer's disease

| PRJNA413544 | ENA

Endotype reversal as a novel strategy for screening drugs targeting familial Alzheimer's disease

Project description:While amyloid-β (Aβ) plaques are considered a hallmark of Alzheimer's disease, clinical trials focused on targeting gamma secretase, an enzyme involved in aberrant Aβ peptide production, have not led to amelioration of AD symptoms or synaptic dysregulation. Screening strategies based on mechanistic, multi-omics approaches that go beyond pathological readouts can aid in the evaluation of therapeutics. Using early-onset Alzheimer's (EOFAD) disease patient lineage PSEN1A246E iPSC-derived neurons, we performed RNA-seq to characterize AD-associated endotypes, which are in turn used as a screening evaluation metric for two gamma secretase drugs, the inhibitor Semagacestat and the modulator BPN-15606.

2022-01-27 | GSE95673 | GEO

Functional aspects of meningeal lymphatics in ageing and Alzheimer's disease [3 of 3]

Project description:Functional aspects of meningeal lymphatics in ageing and Alzheimer's disease [3 of 3]

| PRJNA450860 | ENA

Functional aspects of meningeal lymphatics in ageing and Alzheimer's disease [1 of 3]

Project description:Functional aspects of meningeal lymphatics in ageing and Alzheimer's disease [1 of 3]

| PRJNA411989 | ENA

Functional aspects of meningeal lymphatics in ageing and Alzheimer's disease [2 of 3]

Project description:Functional aspects of meningeal lymphatics in ageing and Alzheimer's disease [2 of 3]

| PRJNA411990 | ENA

Microarray analysis of the astrocyte transcriptome in the ageing brain: relationship to Alzheimer's pathology and ApoE genotype

Project description:Astrocyte dysfunction impacts their normal function, including neuronal support, thereby contributing to neurodegenerative pathologies including Alzheimer's disease (AD). Therefore to understand the role of astrocytes in the pathogenesis of age-related disorders we analysed the gene expression profile of astrocytes with respect to Alzheimer-type pathology. The aim of the present study was to combine immuno-LCM and microarray analysis to characterise the astrocyte transcriptome at different Braak stages, and with respect to ApoE genotype, in post-mortem human temporal cortex sampled dervied from the Medical Research Council Cognitive Function and Ageing Study (MRC-CFAS). GFAP-positive astrocytes were isolated from age, sex and brain pH-matched cases derived from the MRC-CFAS cohort, using immuno laser capture microdissection. The extracted RNA was amplified and applied to HGU133 Plus 2.0 Affymetrix gene arrays. Genes were considered differentially expressed if they showed a minimum 1.5 fold change at p<0.02 in all 6 individual cases in each stage of pathology [18 cases in total: 6 cases Braak stages I-II (3 cases carried at least one ApoE epsilon4 allele and 3 were ApoEe4 negative); 6 cases Braak stages III-IV (3 ApoEe4 positive and 3 ApoEe4 negative; 6 cases Braak stages V-VI (3 ApoEe4 positive and 3 ApoEe4 negative)]. keywords: human GFAP-positive astrocytes

2011-06-01 | E-GEOD-29652 | biostudies-arrayexpress

Hepatocyte polyploidization during ageing protects against transcriptional dysregulation and chronic liver disease

Project description:Single-nucleus RNA-seq2 method allows deep transcriptomic characterization of nuclei isolated from frozen archived tissues. We have used this approach to study the transcriptional profile of individual hepatocytes with different levels of ploidy in young and old wild-type, as well as three other haploinsufficient Mus musculus mice strains. Our data suggest that polyploidisation, a hallmark of ageing in hepatocytes, is also a mechanism by which tetraploid cells are able to buffer genomic perturbations during ageing via non-random allelic segregation of the wild type allele.

2024-07-29 | E-MTAB-12738 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data