Ontology highlight
ABSTRACT:
PROVIDER: PRJNA766517 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16080261.fastq.gz | Fastqsanger.gz | |||
| SRR16080262.fastq.gz | Fastqsanger.gz | |||
| SRR16080263.fastq.gz | Fastqsanger.gz | |||
| SRR16080264.fastq.gz | Fastqsanger.gz | |||
| SRR16080265.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:Mass spectrometry analysis of insoluble proteome from 5xFAD/Mdk-KO mouse brain. This study examines the insoluble protein fraction, focusing on aggregation-prone proteins including Aβ and its associated proteins. The data reveals significant accumulation of Aβ-correlated proteins and microglial components in the absence of MDK, supporting its protective role against amyloid pathology in Alzheimer's disease.
2025-07-16 | PXD061104 | Pride
Project description:Alzheimer's disease (AD) remainsis a prevalent major cause of senile dementia without effective therapeutic strategiesy. Although Recent studies highlight the critical role of microglia has been well accepted to play a critical role in AD pathology, particularly in the early stages, this study is the first breakthrough to show, suggesting that modulation of pathological microglial states represents a therapeutic opportunity. Here we provide evidence that microglial connexin 43 (Cx43) hemichannel is the main switch ofs regulate microglial reactivity in the context of AD, as well as a promising hence presenting a potential therapeutic target. We demonstrated a marked increase in Cx43 protein level in the periplaque microglia in the post-mortem tissue from AD patients. In APPswe/PS1dE9 mouse model, we discoveredfound that microglial Cx43 operates as a hemichannel to influence microglial function, which in turn affects in β-amyloid pathology. Ablation of microglial Cx43 hemichannels by genetic knockout screwed microglia to neuroprotective phenotype by promotinges the microglia-plaque interaction while suppressing the neurotoxic microglial signature, and thereby mitigating the progression of AD. Following this lead, wWe developed a novel formulation of small molecule peptide, treatment strategy employing lipid nanoparticle-delivered molecule TAT-Cx43266-283 (TAT-CX43@LNPs), which selectivespecifically targets blocks Cx43 hemichannels, and conducted a. Our preclinical trialstudy that demonstrated its efficacyeffectiveness in delaying and rescuing β-amyloid-related neuropathology and cognitive impairment in AD mice. This study provides strong evidence to progress our novel drug into clinical trials and translate it not only into a therapeutic agent during disease progression but also offer strong preventive benefits when administered early.
2025-05-22 | GSE272781 | GEO
Project description:Genetic evidence indicates that microglial dysfunctions contribute to the development and progression of various neurologic diseases, emphasizing microglia replacement as a promising therapeutic strategy. However, traditional bone marrow transplantation (BMT) aimed at replenishing brain microglia faces challenges due to low efficiency and potential brain injury from preconditioning with irradiation or chemotherapy. Moreover, the BM-derived cells that migrate to the brain fail to replicate the characteristics of resident microglia. Here, we present a simple yet highly effective microglia transplantation strategy devoid of any conditioning, termed "Tri-Cyclic Microglial Depletion for Transplantation" (TCMDT). This approach leverages three cycles of microglial depletion using the CSF1R inhibitor PLX3397, creating a critical window for the efficient engraftment of exogenous microglia. Notably, transplanting primary cultured microglia via the TCMDT strategy achieves their full restoration to the identity and functions of native microglia. To evaluate the therapeutic potential, we applied our strategy to a Sandhoff disease mouse model, a form of neurodegenerative lysosomal storage disorder (LSD) caused by Hexb deficiency. The results revealed that our strategy facilitated the efficient replacement of deficient microglia, leading to a notable decrease in neurodegeneration and an enhancement in motor performance. Similarly, in an Alzheimer's disease (AD) mouse model carrying the Trem2 R47H mutation, our transplantation strategy corrected microglial dysfunction and alleviated AD-related pathology. Overall, our study presents a practical approach for microglia replacement that is simple, efficient, and safe, offering significant therapeutic potential for treating microglia-associated disorders.
2025-03-06 | GSE272257 | GEO
Project description:Over the past decade, genetic evidence has demonstrated that microglial dysregulation is likely to play a central role in the development of Alzheimer's disease (AD). As resident immune cells in the brain, microglia become dystrophic and senescent during the chronic progression of AD. To explore whether replenishing the brain with new microglia is beneficial to AD, we employed a CSF1R inhibitor PLX3397 to deplete microglia and induce repopulation after the inhibitor withdrawal in 5xFAD transgenic mice. We observed that microglial repopulation ameliorates AD-associated cognitive deficits, accompanied by elevation of synaptic proteins and hippocampal long-term potentiation (LTP). In addition, microglial morphology is restored after microglial self-renewal, and amyloid pathology is reduced with long-term repopulation but not short-term. Transcriptome analysis showed that repopulating microglia in 5xFAD mice recovers a gene expression profile that is highly similar to microglia from WT mice. Notably, the neurotrophic signaling pathway and hippocampal neurogenesis dysregulated in the AD brain are restored after microglial replenishment. At last, we confirmed that microglial repopulation rescues brain-derived neurotrophic factor (BDNF) expression to contribute to synaptic plasticity. Together, we conclude that microglial self-renewal benefits AD brain by restoring the BDNF neurotrophic signaling pathway. Thus, the proper replenishment of microglia may be an effective and novel therapeutic strategy for ameliorating cognition impairment in AD.
2023-07-24 | GSE223156 | GEO
Project description:Proteomic analysis of 5xFAD/Mdk-KO mouse brain reveals proteome-wide changes. This study investigates the impact of midkine (MDK) knockout in 5xFAD mouse model using comprehensive mass spectrometry-based whole proteome profiling. The data demonstrates significant alterations in amyloid formation and microglial activation, providing insights into MDK's protective role in Alzheimer's disease pathology.
2025-07-16 | PXD061103 | Pride
Project description:Targeting microglial Cx43 in Alzheimer's disease
| PRJNA1138724 | ENA
Project description:Aberrant increase of arachidonic acid (ARA) has long been implicated in the pathology of Alzheimer's disease (AD), while the underlying causal mechanism remains unclear. In this study, we revealed a link between ARA mobilization and microglial dysfunction in Aβ pathology. Lipidomic analysis of primary microglia from AppNL-GF mice showed a marked increase in free ARA and lysophospholipids (LPLs) along with a decrease in ARA-containing phospholipids, suggesting increased ARA release from phospholipids (PLs). To manipulate ARA-containing PLs in microglia, we genetically deleted Lysophosphatidylcholine Acyltransferase 3 (Lpcat3), the main enzyme catalyzing the incorporation of ARA into PLs. Loss of microglial Lpcat3 reduced the levels of ARA-containing phospholipids, free ARA and LPLs, leading to a compensatory increase in monounsaturated fatty acid (MUFA)-containing PLs in the AppNL-GF mice. Notably, the reduction of ARA in microglia significantly ameliorated oxidative stress and inflammatory responses while enhancing the phagocytosis of Aβ plaques and promoting the compaction of Aβ deposits. Mechanistically, sc-RNA seq suggested that LPCAT3 deficiency facilitates phagocytosis by facilitating de novo lipid synthesis while protecting microglia from oxidative damage. Collectively, our study reveals a novel mechanistic link between ARA mobilization and microglial dysfunction in AD. Lowering brain ARA levels through pharmacological or dietary interventions may be a potential therapeutic strategy to slow down AD progression.
2024-06-05 | GSE268838 | GEO
Project description:Pathogenic tau accumulation fuels neurodegeneration in Alzheimer’s disease (AD). The role of microglia in tau-driven neurodegeneration is intricate, with DAP12 (DNAX-activation protein 12) triggering microglial immune responses. Mice lacking DAP12 become resistant to tau-induced brain toxicity in tauopathy mice, yet the precise mechanism remains elusive. Our current study uncovers a novel resilience mechanism against tau toxicity conferred by Dap12 deletion. While inactivation of Dap12 elevates tau inclusions, potentially disrupting microglial tau processing, it curbs tau-induced brain inflammation and ameliorates myelin and synapse loss. Tau-induced disease-associated clusters in microglia (MG) and intermediate oligodendrocytes (iOli) are abolished by removal of Dap12. Additionally, AD brains exhibit mouse iOli-like cells spatially correlated with tau pathology. In summary, our study reveals that DAP12 signaling triggers toxic interactions between microglia and oligodendrocytes in tauopathy, mediating tau-induced damage to oligodendrocytes and synaptic loss. Targeting DAP12 signaling presents a promising therapeutic approach for enhancing resilience against tau toxicity in AD.
2025-10-23 | GSE246090 | GEO
Project description:Endotype reversal as a novel strategy for screening drugs targeting familial Alzheimer's disease
| PRJNA377888 | ENA
Project description:Human Microglial State Dynamics in Alzheimer's Disease Progression
| PRJNA944174 | ENA