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MiR-7a-Klf4 axis as a regulator and therapeutic target of neuroinflammation and ferroptosis in Alzheimer's disease

ABSTRACT: The miRNA expression profiling of annotated miRNA in wild type and APP/PSEN1 Tg mouse brain tissue

ORGANISM(S): Mus musculus

PROVIDER: GSE271276 | GEO | 2025/03/24

REPOSITORIES: GEO

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MiR-7a-Klf4 axis as a regulator and therapeutic target of neuroinflammation and ferroptosis in Alzheimer's disease

Project description:MiR-7a-Klf4 axis as a regulator and therapeutic target of neuroinflammation and ferroptosis in Alzheimer's disease

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Comorbidity between Alzheimer’s disease and Major Depression: a behavioural and transcriptomic characterization study in mice

Project description:Background: Major Depression (MD) is the most prevalent psychiatric disease in the population and is considered a prodromal stage of the Alzheimer’s disease (AD). Despite both diseases having a robust genetic component, the common transcriptomic signature remains unknown. Method: In this regard, we investigated the cognitive and emotional behavioural responses in 3- (n=16 per group) and 6-month-old (n=14 per group) in APP/PSEN1-Tg mutant mice, before -amyloid plaques were detected in comparison with non-transgenic mice. Then, we studied the deregulation of genes and pathways in prefrontal cortex, striatum, hippocampus and amygdala of mice at both ages, using transcriptomic and functional data analysis. Results: We found that depressive-like and anxiety-like behaviours, as well as memory impairments are already present at 3-month-old APP/PSEN1-Tg mutant mice together with the deregulation of several genes such as Ciart, Chrm5, Aldh1a, Grin3b, Nr1d1 and Mc4r, and gene sets, including components of the circadian rhythms, electronic transport chain, neuroinflammation and neurotransmission. Then, we extended these results to human data performing GSEA analysis using DisGeNET database, which is specific for diseases and disease-related phenotypes and provides translational support for common deregulated gene sets related to MD and AD. Conclusion: The present study shed further light on the genetic bases shared between MD and AD, illustrating a wide characterization from the behavioural to transcriptomic level in APP/PSEN1-Tg mutant mouse model. These findings could indicate that late MD could be an early manifestation of AD.

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Expression profile of microglia from Egln3–/–, App-Psen1 and App-Psen1

Project description:Microglia was isolated from Egln3–/–; App-Psen1 and App-Psen1 mice using flow cytometry to identify changes in their expression profile and phenotype associated with the absence of Prolyl Hydroxylase 3 (PHD3).

2025-04-15 | GSE97424 | GEO

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Project description:Expression profile of microglia from Egln3–/–, App-Psen1 and App-Psen1

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Forsythoside A Mitigates Alzheimer's-like Pathology by Inhibiting Ferroptosis-mediated Neuroinflammation via Nrf2/GPX4 Axis Activation.

Project description:Ferroptosis and neuroinflammation play crucial roles in Alzheimer's disease (AD) pathophysiology. Forsythoside A (FA), the main constituent of Forsythia suspensa (Thunb.) Vahl., possesses anti-inflammatory, antibacterial, antioxidant, and neuroprotective properties. The present study aimed to investigate the potential role of FA in AD neuropathology using male APP/PS1 double transgenic AD mice, Aβ1-42-exposed N2a cells, erastin-stimulated HT22 cells, and LPS-induced BV2 cells. FA treatment significantly improved mitochondrial function and inhibited lipid peroxidation in Aβ1-42-exposed N2a cells. In LPS-stimulated BV2 cells, FA treatment decreased the formation of the pro-inflammatory factors IL-6, IL-1β, and NO. In male APP/PS1 mice, FA treatment ameliorated memory and cognitive impairments and suppressed Aβ deposition and p-tau levels in the brain. Analyses using proteomics, immunohistochemistry, ELISA, and western blot revealed that FA treatment significantly augmented dopaminergic signaling, inhibited iron deposition and lipid peroxidation, prevented the activation of IKK/IκB/NF-κB signaling, reduced the secretion of pro-inflammatory factors, and promoted the production of anti-inflammatory factors in the brain. FA treatment exerted anti-ferroptosis and anti-neuroinflammatory effects in erastin-stimulated HT22 cells, and the Nrf2/GPX4 axis played a key role in these effects. Collectively, these results demonstrate the protective effects of FA and highlight its therapeutic potential as a drug component for AD treatment.

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Effect of BDNF on the APP transgenic mouse model of Alzheimer's disease

Project description:We examined transgenic (TG) mice expressing human APP695 bearing the double Swedish (671KM>NL) and Indiana (717V>F) amyloid precursor protein (APP) mutations. Lentiviral vectors constitutively expressing BDNF-GFP under control of the CMV/ß-actin hybrid promoter or GFP alone were injected into the entorhinal cortices of TG mice bilaterally at age 6 months, a time point by which neuropathological degeneration and cell loss are established. Age-matched wild-type littermates underwent sham surgery or injection of lentivirus expressing GFP into the entorhinal cortices bilaterally. Keywords: Treatment effect

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DNA methylation profiles across different brain regions in APP/PSEN1 mice

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2015-12-05 | E-GEOD-42745 | biostudies-arrayexpress

Human induced pluripotent stem cells derived from a sporadic Alzheimer's disease patient

Project description:Induced pluripotent stem cell (iPSC) disease models have been generated for a number of diseases, and some have shown their potential utilization for pathological and drug toxicological evaluations. We have generated two hiPSC clones from a non-familial Alzheimerâs patient (AD-iPSCs), which expressed typical undifferentiated markers and fulfilled standard pluripotency assays. Genome-wide microarray analysis revealed that AD-iPSCs are highly similar to control hiPSCs and hESCs, albeit with some noticeable differences in several genes: DNAJC15, GRPR, NAIP and SNORD116-18. Several other biomarkers were differentially expressed in AD-iPSC clones, which were implicated in memory impairment and AD. Furthermore, well characterized familial AD-associated genes (APP, PSEN1, PSEN2) and non-familial (A2M, APOE, GAP43, MAOA, MPO, PLAT, PLAU, SORL1, SNCA) exhibited different expression patterns but were largely reset upon reprogramming into a pluripotent state. Overall, hiPSCs can be good candidates for AD modeling and may represent an in vitro alternative to studying disease mechanisms and drug discovery/toxicology studies. Fibroblasts and two hiPSC clones from a non-familial Alzheimerâs patient (AD-iPSCs) were analyzed. For each cell sample, 2-3 biological replicates were obtained.

2015-12-31 | E-GEOD-31163 | biostudies-arrayexpress

Genome-wide H3K27ac profiles in post-mortem entorhinal cortex samples from Alzheimer's disease cases and controls

Project description:We quantified genome-wide levels of H3K27ac in post-mortem entorhinal cortex tissue samples, identifying widespread Alzheimer's disease (AD)-associated acetylomic variation. Differentially acetylated peaks were identified in the vicinity genes implicated in both tau and amyloid neuropathology (MAPT, APP, PSEN1, PSEN2), as well as genomic regions containing variants associated with sporadic late-onset AD (CR1, TOMM40). Both MAPT and PSEN2 are characterized by an extended hyperacetylated region upstream of the TSS mapping to enhancers in the brain. We show that genes annotated to AD-associated hyper- and hypoacetylated peaks are enriched for brain- and neuropathology-related functions.

2018-08-11 | GSE102538 | GEO

Differential expression analyses in endothelial cells from APP/Psen1 mouse model

Project description:Endothelial cells were isolated by flow cytometry using a specific marker (CD31) and their global gene expression profile was analyzed. CD11b marker was contraselected. This data were used to study molecular mechanisms implicated in endothelial cells from App/Psen1 mouse model. In this dataset, we include the expression data obtained in endothelial cells from APP/Psen1 (18 month-old) mouse model using a specific marker for this cell type (CD31+). Functional enrichment analyses were carried out through GSEA, where we have included specific categories potentially involved with blood vessel formation.

2021-03-22 | GSE121729 | GEO

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