Gene expression profile of sorted CD45+ immune cells from the colons of WT and 5XFAD littermate controlled mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE255819 | GEO | 2025/07/01
REPOSITORIES: GEO
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Project description:Gene expression profile of sorted CD45+ immune cells from the colons of WT and 5XFAD littermate controlled mice
| PRJNA1076580 | ENA
Project description:Alzheimer's disease (AD) is the most common neurodegenerative disease and characterized by the deposition of extracellular amyloid plaques and intracellular neurofibrillary tangles. Although extensive research was performed for Alzheimer's disease (AD) is the most common neurodegenerative disease and characterized by the deposition of extracellular amyloid plaques and intracellular neurofibrillary tangles. Although extensive research was performed for decades, the exact mechanisms and pathological causes of the disease still remain unknown. In order to perform comprehensive and integrative characterization of AD brain, assessment of global proteomic dynamics is required. We performed hippocampal proteome analysis to compare differentially expressed proteins in wild-type and 5XFAD model mice by label-free LC-MS. decades, the exact mechanisms and pathological causes of the disease still remain unknown. In order to perform comprehensive and integrative characterization of AD brain, assessment of global proteomic dynamics is required. We performed hippocampal proteome analysis to compare differentially expressed proteins in wild-type and 5XFAD model mice by label-free LC-MS.
2020-05-26 | PXD012238 | Pride
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:Plaque-associated axonal spheroids (PAAS) are frequently observed around amyloid deposits in Alzheimer's disease (AD) and are known to impair axonal electrical conduction, disrupt neural circuits, and correlate with AD severity. Despite their significance, the mechanisms underlying PAAS formation remain largely unknown. To explore this, we developed a proximity labeling proteomics approach to identify the PAAS proteome in human postmortem brains and mice. Additionally, we established a human iPSC-derived AD model allowing structural, optical electrophysiology, and mechanistic investigation of PAAS pathology. This approach revealed the molecular architecture of PAAS and identified dysregulated biological processes, including protein turnover, cytoskeleton dynamics, and lipid transport. Activated PI3K/AKT/mTOR pathway, which regulates these processes, was expressed in PAAS and strongly correlated with AD severity in humans. Inhibition of mTOR in human iPSC-derived neurons and in mice led to a marked reduction in PAAS. Our study provides a multidisciplinary toolkit for investigating axonal pathology and identifying novel targets for neurodegeneration.
2025-02-20 | PXD048097 | Pride
Project description:Here we analyze the gene expression and chromatin accessibility landscape of immune cells in the brains of 5XFAD mice, a common model of Alzheimer's disease, bearing knock-in of human APOE variants in the mouse APOE locus, and aged to 10, 20, 60, or 96 weeks of age.
2023-12-29 | GSE225503 | GEO
Project description:Alzheimer's disease (AD) is the most common form of dementia in the elderly, affecting cognitive, intellectual, and motor functions. Different hypotheses explain AD’s mechanism, such as the amyloidogenic hypothesis. Moreover, this disease is multifactorial, and several studies have shown that gut dysbiosis and oxidative stress influence its pathogenesis. Knowing that kefir is a probiotic used in therapies to restore dysbiosis and that the bioactive peptides present in it have antioxidant properties, we explored its biotechnological potential as a source of molecules capable of modulating the amyloidogenic pathway and reducing oxidative stress, contributing to the treatment of AD. For that, we used Drosophila melanogaster model for AD (AD-like flies). Identification of bioactive peptides in the kefir sample was made by proteomic and peptidomic analyses, followed by in vitro evaluation of antioxidant and acetylcholinesterase inhibition potential. Flies were treated and their motor performance, brain morphology, and oxidative stress evaluated. Finally, we performed molecular docking between the peptides found and the main pathology-related proteins in the flies. The results showed that the fraction with the higher peptide concentration was positive for the parameters evaluated. In conclusion, these results revealed these kefir peptide-rich fractions have therapeutic potential for AD.
2022-08-11 | PXD034148 | Pride
Project description:Alzheimer's disease (AD) is the most common form of dementia in the elderly, affecting cognitive, intellectual, and motor functions. Different hypotheses explain AD’s mechanism, such as the amyloidogenic hypothesis. Moreover, this disease is multifactorial, and several studies have shown that gut dysbiosis and oxidative stress influence its pathogenesis. Knowing that kefir is a probiotic used in therapies to restore dysbiosis and that the bioactive peptides present in it have antioxidant properties, we explored its biotechnological potential as a source of molecules capable of modulating the amyloidogenic pathway and reducing oxidative stress, contributing to the treatment of AD. For that, we used Drosophila melanogaster model for AD (AD-like flies). Identification of bioactive peptides in the kefir sample was made by proteomic and peptidomic analyses, followed by in vitro evaluation of antioxidant and acetylcholinesterase inhibition potential. Flies were treated and their motor performance, brain morphology, and oxidative stress evaluated. Finally, we performed molecular docking between the peptides found and the main pathology-related proteins in the flies. The results showed that the fraction with the higher peptide concentration was positive for the parameters evaluated. In conclusion, these results revealed these kefir peptide-rich fractions have therapeutic potential for AD.
2022-08-11 | PXD034190 | Pride
Project description:Alzheimer's disease (AD) is the most common form of dementia in the elderly, affecting cognitive, intellectual, and motor functions. Different hypotheses explain AD’s mechanism, such as the amyloidogenic hypothesis. Moreover, this disease is multifactorial, and several studies have shown that gut dysbiosis and oxidative stress influence its pathogenesis. Knowing that kefir is a probiotic used in therapies to restore dysbiosis and that the bioactive peptides present in it have antioxidant properties, we explored its biotechnological potential as a source of molecules capable of modulating the amyloidogenic pathway and reducing oxidative stress, contributing to the treatment of AD. For that, we used Drosophila melanogaster model for AD (AD-like flies). Identification of bioactive peptides in the kefir sample was made by proteomic and peptidomic analyses, followed by in vitro evaluation of antioxidant and acetylcholinesterase inhibition potential. Flies were treated and their motor performance, brain morphology, and oxidative stress evaluated. Finally, we performed molecular docking between the peptides found and the main pathology-related proteins in the flies. The results showed that the fraction with the higher peptide concentration was positive for the parameters evaluated. In conclusion, these results revealed these kefir peptide-rich fractions have therapeutic potential for AD.
2022-08-11 | PXD034189 | Pride
Project description:islation of AD mitochondrial and then detect the changes
2022-04-03 | PXD032992 |
Project description:Sodium oligomannate (GV-971), an oligosaccharide drug approved in China for treating mild-to-moderate Alzheimer's disease (AD), was previously found to recondition the gut microbiota and limit altered peripheral Th1 immunity in AD transgenic mice. As a follow-up study, we here provide advances by pinpointing a Lactobacillus murinus strain that highly expressed a gene encoding a putative adhesin containing Rib repeats (Ribhigh-L.m.) that was particularly enriched in 5XFAD transgenic mice. Mechanistically, Ribhigh-L.m. adherence to the gut epithelia upregulated fecal metabolites, among which lactate ranked as the top candidate. Lactate stimulated the epithelial production of serum amyloid A (SAA) in gut via GPR81-NFκB axis, contributing to peripheral Th1 activation. Moreover, GV-971 disrupted the adherence of Ribhigh-L.m. to gut epithelia via directly binding to Rib, leading to the reduced SAA and alleviated Th1-skewed inflammation. These findings were replicated in early-staged AD patients. Together, we gained further insights between gut bacteria and AD progression and the mechanism of GV-971 in treating AD.
2024-11-20 | GSE247212 | GEO