Ontology highlight
ABSTRACT:
PROVIDER: PRJNA897115 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22163955_1.fastq.gz | Fastqsanger.gz | |||
| SRR22163955_2.fastq.gz | Fastqsanger.gz | |||
| SRR22163956_1.fastq.gz | Fastqsanger.gz | |||
| SRR22163956_2.fastq.gz | Fastqsanger.gz | |||
| SRR22163957_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 30 |
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Project description:The pathological aggregation of Tau protein into oligomers and fibrils plays a central role in Alzheimer's disease (AD). Here, we explore the biochemical and cellular properties conferred by a unique 19-amino acid intronic peptide found exclusively in the Tau11i isoform. We demonstrate that this intronic peptide mediates robust formation of high molecular weight (HMW) oligomers that resist denaturing and reducing conditions, distinguishing Tau11i from other Tau isoforms lacking this sequence. Tau11i also uniquely forms stable heterodimers with Tau441, suggesting a role in the propagation of Tau pathology. Additionally, the intronic peptide enhances Tau11i’s liquid-liquid phase separation (LLPS), a critical early event associated with pathological aggregation. In vitro assays showed that Tau11i aggregates into β-sheet-rich fibrils more efficiently than other Tau isoforms, significantly facilitating fibril formation and cellular seeding in Tau biosensor cells. Transcriptomic profiling indicated substantial dysregulation in neuronal pathways involving immune response, synaptic function, and metabolism, with Tau11i-expressing neurons closely mirroring the gene expression patterns of AD neurons, particularly the AT8-negative subtype. Furthermore, Tau11i specifically interacts with stress granule-associated RNA-binding proteins, notably PABPC1, implicating it in stress granule dynamics and RNA homeostasis. Collectively, these findings identify the intronic peptide as a critical factor driving Tau11i-specific oligomerization and early-stage molecular alterations associated with Alzheimer's disease, highlighting its potential as a novel therapeutic target distinct from classic Tau pathology.
2025-12-26 | GSE294848 | GEO
Project description:To investigate whether PS19 brain lysate transfection changes ER stress gene expression in Biosensor cell
2022-12-22 | GSE217525 | GEO
Project description:Many RNA-binding proteins (RBPs), particularly those associated with RNA granules, promote pathological protein aggregation in neurodegenerative diseases. Here, we demonstrate that G3BP2, a core component of stress granules, directly interacts with Tau and inhibits Tau aggregation. In the human brain, the interaction of G3BP2 and Tau is dramatically increased in multiple Tauopathies and precedes neurofibrillary tangle (NFT) formation in Alzheimer’s disease (AD). Surprisingly, Tau pathology is significantly elevated upon loss of G3BP2 in human neurons and brain organoids. Moreover, we find that G3BP2 masks the microtubule-binding region (MTBR) of Tau, thereby inhibiting Tau aggregation. Our study defines a novel role for RBPs as a line of defense against Tau aggregation in Tauopathies.
2023-05-17 | GSE226624 | GEO
Project description:Protein aggregation, impaired degradation, and immune activation are central hallmarks of many neurodegenerative diseases, yet how these processes are coordinated remain unclear. Here we identify a new class of phase-separated proteostasis organelles, termed immune degradation condensates (IDCs), composed of BAG2 assemblies. Inflammatory cues drive the formation of BAG2 IDCs, which are enriched in immunoproteasome components, major histocompatibility complex class I (MHC-I) peptide-loading machinery, and chaperones associated with the endoplasmic reticulum (ER). These assemblies redirect proteostatic cargo from centrosomal aggregation pathways to immune-specialized sites, coupling substrate clearance to antigenic peptide production and enhancing CD8⁺ T cell engagement. Using a cellular model of aggregation-prone Tau, we show that BAG2 IDCs capture pathological Tau fibrils at ER–microtubule interfaces and process them into antigenic peptides, thereby reducing the abundance of the aggregation-prone PHF6 motif. We term this system the Proteostasis-Associated Immune Relay (PAIR), establishing IDCs as critical hubs with potential implications for multiple disease states.
2026-04-08 | GSE326781 | GEO
Project description:Treatment of MCF7 breast cancer cells by cisplatin leads to a very specific metabolic response and an onset of cell death about 10-11 h after beginning of treatment. For more detailed understanding of the molecular processes underlying the specific metabolic response, mRNA was isolated from MCF7 cells when the specific changes, (i) induction of glycolysis and (ii) onset of cell death, were detected during online measurement in the cell biosensor system. MCF7 breast cancer cells were treated with cisplatin in the BIONAS 2500 cell biosensor chip system, and samples were collected from the biosensor chip module at time points when glycolysis was induced (change of ph; 8-9h) and at the beginning of cell death (change of impedance; 10-11h).
2011-04-04 | E-GEOD-28274 | biostudies-arrayexpress
Project description:Tau aggregation in neurofibrillary tangles (NFTs) is closely associated with neurodegeneration and cognitive decline in Alzheimer’s disease (AD). However, the molecular signatures that distinguish between aggregation-prone and aggregation-resistant cell states are unknown. We developed methods for the high-throughput isolation and transcriptome profiling of single somas with NFTs fro¬m human AD brain, quantified the susceptibility of 20 neocortical subtypes for NFT formation and death, and identified both shared and cell-type-specific signatures. NFT-bearing neurons shared a marked upregulation of synaptic transmission-related genes, including a core set of 63 genes enriched for synaptic vesicle cycling. Oxidative phosphorylation and mitochondrial dysfunction were highly cell-type dependent. Apoptosis was only modestly enriched, and the susceptibilities of NFT-bearing and NFT-free neurons for death were highly similar. Our analysis suggests that NFTs represent cell-type-specific responses to stress and synaptic dysfunction. We provide a resource for biomarker discovery and the investigation of tau-dependent and tau-independent mechanisms of neurodegeneration.
2020-08-05 | GSE129308 | GEO
Project description:Yuraszeck2010 - Vulnerabilities in the Tau
Network in Tau Pathophysiology
This model is described in the article:
Vulnerabilities in the tau
network and the role of ultrasensitive points in tau
pathophysiology.
Yuraszeck TM, Neveu P,
Rodriguez-Fernandez M, Robinson A, Kosik KS, Doyle FJ 3rd.
PLoS Comput. Biol. 2010; 6(11):
e1000997
Abstract:
The multifactorial nature of disease motivates the use of
systems-level analyses to understand their pathology. We used a
systems biology approach to study tau aggregation, one of the
hallmark features of Alzheimer's disease. A mathematical model
was constructed to capture the current state of knowledge
concerning tau's behavior and interactions in cells. The model
was implemented in silico in the form of ordinary differential
equations. The identifiability of the model was assessed and
parameters were estimated to generate two cellular states: a
population of solutions that corresponds to normal tau
homeostasis and a population of solutions that displays
aggregation-prone behavior. The model of normal tau homeostasis
was robust to perturbations, and disturbances in multiple
processes were required to achieve an aggregation-prone state.
The aggregation-prone state was ultrasensitive to perturbations
in diverse subsets of networks. Tau aggregation requires that
multiple cellular parameters are set coordinately to a set of
values that drive pathological assembly of tau. This model
provides a foundation on which to build and increase our
understanding of the series of events that lead to tau
aggregation and may ultimately be used to identify critical
intervention points that can direct the cell away from tau
aggregation to aid in the treatment of tau-mediated (or
related) aggregation diseases including Alzheimer's.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000542.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000542 | BioModels
Project description:Aggregation of the microtubule-associated protein, tau, can lead to neurofibrillary tangle formation in neurons and glia, the hallmark of tauopathy. The cellular damages induced by the tau overexpression and aggregation may lead to multiple pathologic features of tauopathy. However, the effect of aging on tauopathy has not been elucidated yet. Here, we conducted lncRNA/mRNA sequencing analysis on P301S mutant Tau transgenic mouse model (PS19) with different ages to track the genetic changes occurred by the aging and progression of tau overexpression.
2019-06-23 | GSE118473 | GEO
Project description:Transcriptome profile of Dictyostelium cell during ER-stress
| PRJNA412540 | ENA
Project description:Tauopathies, such as Alzheimer’s disease and Frontotemporal Dementia, are common neurodegenerative diseases characterized by misfolding, hyperphosphorylation, and aggregation of Tau. Molecular mechanisms underlying Tauopathies are still poorly understood, which is in part due to a lack of human models autonomously developing major disease hallmarks. Formation of late-stage disease phenotypes may require adult Tau isoform expression, which contributes to Tau pathogenesis but is challenging to replicate in human stem-cell-derived systems, thus impeding research on underlying mechanisms and drug development. Here we show that induction of adult human brain-like 4R Tau isoform expression enables cell-intrinsic formation of late-stage Tauopathy hallmarks in iPSC-derived neurons engineered to contain synergistic Tau mutations, without exogenous sources of Tau pathology. Neurons accumulated seeding-competent, hyper-phosphorylated, fibrillar Tau in tangle-like structures. Furthermore, exclusive expression of mutant 4R in the absence of the 3R Tau isoform disproportionately intensified pathology, resulting in highly abundant Tau misfolding and aggregation. Finally, we provide proof-of-principle that our model can be translationally applied both to test chemical disease modulators and evaluate human Tau PET tracers. Collectively, our model corroborates the central role of 4R Tau isoform expression for pathogenesis in human neurons and enables novel investigations to elucidate mechanisms underlying human Tauopathy formation. Moreover, it may also serve as a platform supporting urgently needed development of disease-modifying drugs.
2026-01-26 | GSE311009 | GEO