Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA318382 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive deterioration of cognitive function. Evidence suggests a role for epigenetic regulation, in particular the cytosine modifications 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC,) in AD. 5hmC is highly enriched in the nervous system and displays neurodevelopment and age-related changes. To determine the role of 5hmC in AD, we performed genome-wide analyses of 5hmC in DNA from prefrontal cortex of post-mortem AD as well as RNA-Seq to correlate changes in methylation status with transcriptional changes. We also utilized the existing AD fly model to further test the functional significance of these epigenetically altered loci. We identified 325 genes containing differentially hydroxymethylated loci (DhMLs) in both the discovery and replication datasets, and these are enriched for pathways involved in neuron projection development and neurogenesis. Of the 325 genes identified, 140 also showed changes in gene expression by RNA-Seq. Proteins encoded by genes identified in the current analysis form direct protein-protein interactions with AD-associated genes, expanding the network of genes implicated in AD. Furthermore, we identified AD-associated single nucleotide polymorphisms (SNPs) located within or near DhMLs, suggesting that these SNPs may identify regions of epigenetic gene regulation that play a role in AD pathogenesis. Finally using the existing AD fly model we showed that some of these genes could modulate the toxicity associated with AD. Our data implicate neuron projection development and neurogenesis pathways as potential targets in AD. These results indicate that incorporating epigenomic and transcriptomic data with GWAS data can expand the known network of genes involved in disease pathogenesis. Combination of epigenome profiling and Drosophila model enables us to identify the epigenetic modifiers of Alzheimer's disease. University of Kentucky Alzheimer's Disease Research Center (3 control, 3 Alzheimer's) and Emory University Alzheimer's Disease Research Center (2 control, 2 Alzheimer's)
2016-07-20 | E-GEOD-72782 | biostudies-arrayexpress
Project description:Glucose hypometabolism is one of the major characteristics of Alzheimer's disease (AD). The energy deficiency in AD brain has been at least partially attributed to accelerated mitochondrial dysfunction than normal aging. In earlier publications, we have shown that small molecule mitochondrial complex I inhibitor CP2 facilitated mitochondrial regeneration and rescued mitochondrial deficiency in familial AD mice model APP-PS1. Here in this study, we investigated whether a typical mitochondrial deficiency mouse model could recapitulate molecular expression signatures of AD brain and whether CP2 was able to rescue the AD brain phenotype. Ndufs4 is one of the regulatory subunits of mitochondria complex I. Knockout of Ndufs4 resulted in complex I assembly failure and approximately half mitochondrial function loss. Ndufs4-knockout mice are viable but are short in lifespan (up to about 90 days). This model has been previously used to study Leigh syndrome, a heritable mitochondrial deficiency disease. In this dataset, we performed RNAseq on brains of CP2 treated Ndufs4-knockout mice and examined the expression changes upon CP2 treatment.
2023-12-01 | GSE242286 | GEO
Project description:Expression data from the neuron model of Alzheimer's disease (AD) with or without treatment of recombinant human mitochondrial transcriptional factor A (rhTFAM) protein
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Project description:Expression data from Alzheimer's disease model mouse
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Project description:Expression data from the neuron model of Alzheimer's disease (AD)
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Project description:Ligand activation of nuclear receptor has been linked with therapeutic implications in Alzheimer's Disease. In this study, we used AD mouse model treated with Bexarotene, an RXR agonist and performed scRNA-seq and snATAC-seq using the brain tissue. We reavealed changes in chromatin architure in brain of AD-lie mouse model in response to RXR ligand and link those changes to the initiation of transcriptional programs at a single-cell resolution.
2025-12-11 | GSE289039 | GEO
Project description:Ligand activation of nuclear receptor has been linked with therapeutic implications in Alzheimer's Disease. In this study, we used AD mouse model treated with Bexarotene, an RXR agonist and performed scRNA-seq and snATAC-seq using the brain tissue. We reavealed changes in chromatin architure in brain of AD-lie mouse model in response to RXR ligand and link those changes to the initiation of transcriptional programs at a single-cell resolution.
2025-12-31 | GSE283905 | GEO
Project description:Ligand activation of nuclear receptor has been linked with therapeutic implications in Alzheimer's Disease. In this study, we used AD mouse model treated with Bexarotene, an RXR agonist and performed scRNA-seq and snATAC-seq using the brain tissue. We reavealed changes in chromatin architure in brain of AD-lie mouse model in response to RXR ligand and link those changes to the initiation of transcriptional programs at a single-cell resolution.
2025-12-11 | GSE283906 | GEO
Project description:Emerging small noncoding RNAs (sncRNAs), including tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNAs), are critical in diverse biological processes, such as neurological diseases. Traditional sncRNA-seq protocols often miss these sncRNAs due to their modifications. We have recently developed PANDORA-seq, a method enabling more comprehensive detection of modified sncRNAs by overcoming the RNA modifications. Using PANDORA-seq, we have revealed an updated sncRNA profile enriched by tsRNAs/rsRNAs in the mouse cortex and found a particularly significant downregulation of mitochondrial tsRNAs and rsRNAs in an Alzheimer's disease (AD) mouse model, compared to genomic tsRNAs and rsRNAs. Moreover, our integrated analysis of cortex gene expression and sncRNA profiles reveals that those downregulated mitochondrial sncRNAs are negatively correlated with enhanced lysosomal activity, suggesting a crucial interplay between mitochondrial RNA dynamics and lysosomal function in AD. Given the versatile tsRNA/tsRNA molecular actions in cellular regulation, our data provides insights for future mechanistic study of AD with potential therapeutic strategies.
2024-12-17 | GSE277483 | GEO
Project description:CDKN2A/p16INK4a is a canonical marker of cellular senescence and is implicated in aging-related neurodegenerative diseases, including Alzheimer's disease (AD). Yet, how neuronal p16INK4a contributes to neurodegeneration remains unclear, as prior research has largely focused on glial roles . Here, we show that p16INK4a is selectively upregulated in hippocampal granule neurons of AD patient brains and mouse models. Mechanistically, p16INK4a directly binds to GTF2H1, a core subunit of the transcription factor IIH (TFIIH) complex, sterically hindering GTF2H1–RNA polymerase II assembly. This disruption causes genome-wide transcriptional stalling, with preferential downregulation of mitochondrial electron transport chain genes. Notably, p16INK4a overexpression stalls transcription of NDUFB9, a subunit of mitochondrial respiratory complex I, inducing mitochondrial dysfunction and neuronal energy deficits. Hipocampal p16Ink4a overexpression impairs synaptic plasticity and memory in wild-type mice and exacerbates cognitive decline in AD mice, whereas its knockdown restores transcriptional activity, synaptic function, and memory performance. These findings identify a previously unrecognized p16INK4a-mediated cascade linking neuronal senescence to neurodegeneration and establish p16INK4a as an active driver of synaptic dysfunction via direct inhibition of core transcriptional machinery. Targeting the p16INK4a–GTF2H1 interaction may thus offer a therapeutic strategy for AD.
2026-08-19 | GSE305454 | GEO