Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Apolipoprotein E2 protects against aging-induced neuronal endosomal dysfunction through enhanced exosome secretion

ABSTRACT: Apolipoprotein E2 protects against aging-induced neuronal endosomal dysfunction through enhanced exosome secretion

PROVIDER: PRJNA778111 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR16805700.fastq.gz	Fastqsanger.gz
	SRR16805701.fastq.gz	Fastqsanger.gz
	SRR16805648.fastq.gz	Fastqsanger.gz
	SRR16805649.fastq.gz	Fastqsanger.gz
	SRR16805650.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 54

Similar Datasets

Apolipoprotein E2 protects against aging-induced neuronal endosomal dysfunction through enhanced exosome secretion

Project description:In 12-month-old APOE targeted-replacement mice, we report that overall differences in gene expression were the most prominent when comparing the protective APOE2 to the other two alleles, with fewer differences found when comparing the risk-neutral APOE3 and disease-promoting APOE4 alleles. When compared with either APOE3 or APOE4, differential expression of genes within the endosomal pathways is a prominent feature of APOE2 expression in the brain. We hypothesized that the protective effects of APOE2 are mediated through the endosomal pathway during aging. In contrast to Alzheimer’s disease and APOE4 models, we detected normal morphology and abundance of early endosomes within cortical neurons of APOE2 targeted-replacement mice during aging despite decreased rab5b recruitment to early endosomes. Similarly, the morphology and abundance of retromer-associated vesicles was normal in APOE2 mice, despite reduced recruitment of vesicle-associated VPS35. Significantly, we observed increased brain extracellular levels of endosome-derived exosomes in APOE2 compared with APOE3 mice during aging, indicative of an enhanced endosomal cargo clearance to the extracellular space that contributes to a homeostatic balance of endosomal functions. Our findings thus demonstrate that APOE2 effectively offsets endosomal pathway changes during aging to preserve its integrity by enhancing exosome biogenesis, mitigating age-driven endosomal dysfunction that contributes to Alzheimer’s disease risk.

2023-07-31 | GSE188267 | GEO

Apolipoprotein E2 expression drives increased brain exosome levels during aging to mitigate neuronal endosomal dysfunction

Project description:Apolipoprotein E2 expression drives increased brain exosome levels during aging to mitigate neuronal endosomal dysfunction

| PRJNA982803 | ENA

Apolipoprotein E2 expression drives increased brain exosome levels during aging to mitigate neuronal endosomal dysfunction

Project description:The polymorphic APOE gene is the greatest genetic determinant of sporadic Alzheimer’s disease risk: the APOE4 allele increases risk while the APOE2 allele is neuroprotective compared with the risk-neutral APOE3 allele. The neuronal endosomal system is inherently vulnerable during aging, and APOE4 exacerbates this vulnerability by driving an enlargement of early endosomes and reducing exosome release in humans and mice. We hypothesized that the protective effects of APOE2 are mediated through the endosomal pathway during aging. In contrast to Alzheimer’s disease and APOE4 models, we detected normal morphology and abundance of early endosomes within cortical neurons of APOE2 targeted-replacement mice during aging despite decreased rab5b recruitment to early endosomes. Similarly, the morphology and abundance of retromer-associated vesicles was normal in APOE2 mice, despite reduced recruitment of vesicle-associated VPS35. Significantly, we observed increased brain extracellular levels of endosome-derived exosomes in APOE2 compared with APOE3 mice during aging, indicative of an enhanced endosomal cargo clearance to the extracellular space that contributes to a homeostatic balance of endosomal functions. Our findings thus demonstrate that APOE2 effectively offsets endosomal pathway changes during aging to preserve its integrity by enhancing exosome biogenesis, mitigating age-driven endosomal dysfunction that contributes to Alzheimer’s disease risk.

2024-06-05 | GSE234711 | GEO

Sulfisoxazole inhibits exosome secretion for potential breast cancer treatment

Project description:Inhibitors of the secretion of cancer exosomes, which promote cancer progression and metastasis, can not only accelerate exosome biology research but also offer therapeutic benefits for cancer patients. We identified sulfisoxazole (SFX) which inhibits exosome secretion from breast cancer cells. SFX, an FDA-approved oral antibiotic, showed significant anti-tumor and anti-metastatic effects in mouse models of breast cancer xenografts, reduced the expression of proteins involved in exosome biogenesis and secretion, and triggered co-localization of multivesicular endosomes (MVEs) with lysosomes for degradation. These findings provide a foundation for exosome-targeted cancer therapies and the mechanistic studies on exosome biology.

2019-11-13 | PXD012689 | Pride

MUC1-C IS A MASTER REGULATOR OF MICA/B NKG2D LIGAND AND EXOSOME SECRETION IN HUMAN CANCER CELLS

Project description:MUC1-C regulates expression of MICA/B NKG2D LIGAND AND enhance EXOSOME SECRETION IN HUMAN CANCER CELLS

2022-10-17 | GSE215308 | GEO

Human hepatoma Huh-7 cell culture models deficient in apolipoprotein B secretion

Project description:Human hepatoma Huh-7 cell culture models deficient in apolipoprotein B secretion

| PRJNA1124159 | ENA

Src in endosomal membranes promotes exosome secretion and tumor progression.

Project description:c-Src is a membrane-associated tyrosine kinase that has key roles in the signaling transduction that controls cell growth, adhesion, and migration. In the early stage of carcinogenesis, c-Src is activated under the plasma membrane and transduces oncogenic signals. Here we show that c-Src localized to the endosomal membrane has unique functions in c-Src-transformed cells. Our results indicate that activated c-Src in the endosomal membrane promoted the secretion of exosomes, in which c-Src was encapsulated. In addition, the ESCRT-interacting molecule, Alix was identified as a c-Src-interacting protein in exosomes. We revealed that the interaction between the SH3 domain of c-Src and the proline-rich region of Alix activates ESCRT-mediated intra-luminal vesicle (ILV) formation, resulting in the upregulation of exosome secretion in c-Src-transformed cells. We observed also a correlation between malignant phenotypes and Alix-dependent aberrant exosome secretion in Src-upregulated cancer cells. Collectively, our findings provide a unique mechanism for the upregulation of exosomes in cancer cells, as well as new insights into the significance of exosome secretion in cancer progression.

| S-EPMC6397170 | biostudies-literature

Human hepatoma Huh-7 cell culture models deficient in apolipoprotein B secretion

Project description:High plasma apolipoprotein B (apoB)-containing lipoproteins are both a biomarker and causal mediator of many metabolic diseases. Inhibition of apoB and MTP decreases plasma lipid levels but at a risk of lipid accumulation in tissues. Whole body knock out of MTP and APOB are embronically lethal. Therefore, we created a human hepatome cells line (Ako) deficient in APOB gene to understand the global consequences of APOB loss. APOB gene deletion significantly reduced apoB mRNA and protein levels in the Ako cells compared to control cells. These cells supported apoB48 secretion when transfected with apoB48 expression plasmids. These cells did not accumulate significant amounts of triglyceride. KEGG pathway analysis of RNA-Seq data showed a significant increase in DNA replication/repair pathway and complement/coagulation cascade in the Ako cells. The most downregulated pathways included the PI3k-Akt signaling and MAPK signaling pathways. Total proteome analysis of secretory proteins identifed Vitamin D binding protein as the most upregulated protein while apoB was the most dowregulated protein in these cells. Since both APOB and MTP are important part of the lipoprotein assmebly and secretion, we also perfrmed total transcriptome analysis for the MTP deficient Huh-7 (Mko-3) cells. We found differential expression of some the pathways in both Ako and Mko-3 cells such as DNA replication, base excision repair, steroid hormone biosynthesis and pathways reated to breast cancer. These cells may be useful in studying structure-function analysis of apoB peptides and to address the cellular consequences of disruptions in lipoprotein assembly and secretion. However; further detailed studies are needed to establish how apoB regulates these pathways

2025-07-23 | GSE269949 | GEO

PTEN facilitates lysosome biogenesis and decreases exosome secretion by directly dephosphorylating TFEB

Project description:PTEN facilitates lysosome biogenesis and decreases exosome secretion by directly dephosphorylating TFEB

| PRJNA893213 | ENA

Aeromonas hydrophila E2 strain:E2

Project description:Aeromonas hydrophila E2 strain:E2 Genome sequencing

| PRJNA186552 | ENA