RNA-seq analysis of CREB3L2 dimers in Hippocampal Neurons
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE169185 | GEO | 2023/03/03
REPOSITORIES: GEO
Similar Datasets
Project description:RNA-seq analysis of CREB3L2 dimers in Hippocampal Neurons
| PRJNA715494 | ENA
Project description:Alternative splicing (AS) is the main process that amplifies DNA information and is a crucial target of signaling cascades resulting from UV irradiation of human cells. The specific impact of UV-induced cyclobutane pyrimidine dimers (CPDs) at the transcriptional and AS levels has not been addressed. By using a CPD photolyase, a flavoenzyme that directly reverts CPDs, we analyze the contribution of this lesion to the expression program in human keratinocytes.
2017-04-17 | GSE85510 | GEO
Project description:Late-onset Alzheimer disease (LOAD) is the most common neurodegenerative disorder worldwide. Recent studies have shown that differential expression in genes (DEG) related to inflammatory response may result associated with disease onset and progression. This study aimed to explore the molecular pathogenesis of LOAD-related inflammation through next-generation sequencing, to assess RNA expression profiles in Alzheimer's disease patients and healthy controls.
2021-03-13 | GSE168813 | GEO
Project description:Proctor2012 - Amyloid-beta aggregation
This model supports the current thinking that levels of dimers are important in initiating the aggregation process.
This model is described in the article:
Aggregation, impaired degradation and immunization targeting of amyloid-beta dimers in Alzheimer's disease: a stochastic modelling approach.
Proctor CJ, Pienaar IS, Elson JL, Kirkwood TB
Molecular Neurodegeneration. 2012; 7:32
Abstract:
BACKGROUND:
Alzheimer's disease (AD) is the most frequently diagnosed neurodegenerative disorder affecting humans, with advanced age being the most prominent risk factor for developing AD. Despite intense research efforts aimed at elucidating the precise molecular underpinnings of AD, a definitive answer is still lacking. In recent years, consensus has grown that dimerisation of the polypeptide amyloid-beta (Aß), particularly Aß₄₂, plays a crucial role in the neuropathology that characterise AD-affected post-mortem brains, including the large-scale accumulation of fibrils, also referred to as senile plaques. This has led to the realistic hope that targeting Aß₄₂ immunotherapeutically could drastically reduce plaque burden in the ageing brain, thus delaying AD onset or symptom progression. Stochastic modelling is a useful tool for increasing understanding of the processes underlying complex systems-affecting disorders such as AD, providing a rapid and inexpensive strategy for testing putative new therapies. In light of the tool's utility, we developed computer simulation models to examine Aß₄₂ turnover and its aggregation in detail and to test the effect of immunization against Aß dimers.
RESULTS:
Our model demonstrates for the first time that even a slight decrease in the clearance rate of Aß₄₂ monomers is sufficient to increase the chance of dimers forming, which could act as instigators of protofibril and fibril formation, resulting in increased plaque levels. As the process is slow and levels of Aβ are normally low, stochastic effects are important. Our model predicts that reducing the rate of dimerisation leads to a significant reduction in plaque levels and delays onset of plaque formation. The model was used to test the effect of an antibody mediated immunological response. Our results showed that plaque levels were reduced compared to conditions where antibodies are not present.
CONCLUSION:
Our model supports the current thinking that levels of dimers are important in initiating the aggregation process. Although substantial knowledge exists regarding the process, no therapeutic intervention is on offer that reliably decreases disease burden in AD patients. Computer modelling could serve as one of a number of tools to examine both the validity of reliable biomarkers and aid the discovery of successful intervention strategies.
This model is hosted on BioModels Database
and identified by: BIOMD0000000462
.
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 | BIOMD0000000462 | BioModels
Project description:Cancer-related alterations of the p53 Tetramerization Domain (TD) abrogate wild-type (WT) p53 function. They result in a protein that preferentially forms monomers or dimers. These are also normal p53 states under basal cellular conditions. However, their physiological relevance is not well understood. We have established in vivo models for monomeric and dimeric p53 which model Li-Fraumeni Syndrome patients with germline p53 TD alterations. p53 monomers are inactive forms of the protein. Unexpectedly, p53 dimers conferred some tumor suppression that is not mediated by canonical WT p53 activities. p53 dimers upregulate the PPAR pathway. These activities are associated with lower prevalence of thymic lymphomas and inhibition of CD8+ T-cell accumulation. Lymphomas derived from dimeric p53 mice show cooperating alterations in the PPAR pathway, further implicating a role for these activities in tumor suppression. Our data reveal novel functions for p53 dimers and support the exploration of PPAR agonists as therapies.
2023-03-01 | GSE220964 | GEO
Project description:Cancer-related alterations of the p53 Tetramerization Domain (TD) abrogate wild-type (WT) p53 function. They result in a protein that preferentially forms monomers or dimers. These are also normal p53 states under basal cellular conditions. However, their physiological relevance is not well understood. We have established in vivo models for monomeric and dimeric p53 which model Li-Fraumeni Syndrome patients with germline p53 TD alterations. p53 monomers are inactive forms of the protein. Unexpectedly, p53 dimers conferred some tumor suppression that is not mediated by canonical WT p53 activities. p53 dimers upregulate the PPAR pathway. These activities are associated with lower prevalence of thymic lymphomas and inhibition of CD8+ T-cell accumulation. Lymphomas derived from dimeric p53 mice show cooperating alterations in the PPAR pathway, further implicating a role for these activities in tumor suppression. Our data reveal novel functions for p53 dimers and support the exploration of PPAR agonists as therapies.
2023-03-01 | GSE220965 | GEO
Project description:Cancer-related alterations of the p53 Tetramerization Domain (TD) abrogate wild-type (WT) p53 function. They result in a protein that preferentially forms monomers or dimers. These are also normal p53 states under basal cellular conditions. However, their physiological relevance is not well understood. We have established in vivo models for monomeric and dimeric p53 which model Li-Fraumeni Syndrome patients with germline p53 TD alterations. p53 monomers are inactive forms of the protein. Unexpectedly, p53 dimers conferred some tumor suppression that is not mediated by canonical WT p53 activities. p53 dimers upregulate the PPAR pathway. These activities are associated with lower prevalence of thymic lymphomas and inhibition of CD8+ T-cell accumulation. Lymphomas derived from dimeric p53 mice show cooperating alterations in the PPAR pathway, further implicating a role for these activities in tumor suppression. Our data reveal novel functions for p53 dimers and support the exploration of PPAR agonists as therapies.
2023-03-01 | GSE220963 | GEO
Project description:Cancer-related alterations of the p53 Tetramerization Domain (TD) abrogate wild-type (WT) p53 function. They result in a protein that preferentially forms monomers or dimers. These are also normal p53 states under basal cellular conditions. However, their physiological relevance is not well understood. We have established in vivo models for monomeric and dimeric p53 which model Li-Fraumeni Syndrome patients with germline p53 TD alterations. p53 monomers are inactive forms of the protein. Unexpectedly, p53 dimers conferred some tumor suppression that is not mediated by canonical WT p53 activities. p53 dimers upregulate the PPAR pathway. These activities are associated with lower prevalence of thymic lymphomas and inhibition of CD8+ T-cell accumulation. Lymphomas derived from dimeric p53 mice show cooperating alterations in the PPAR pathway, further implicating a role for these activities in tumor suppression. Our data reveal novel functions for p53 dimers and support the exploration of PPAR agonists as therapies.
2023-03-01 | GSE220962 | GEO
Project description:Cancer-related alterations of the p53 Tetramerization Domain (TD) abrogate wild-type (WT) p53 function. They result in a protein that preferentially forms monomers or dimers. These are also normal p53 states under basal cellular conditions. However, their physiological relevance is not well understood. We have established in vivo models for monomeric and dimeric p53 which model Li-Fraumeni Syndrome patients with germline p53 TD alterations. p53 monomers are inactive forms of the protein. Unexpectedly, p53 dimers conferred some tumor suppression that is not mediated by canonical WT p53 activities. p53 dimers upregulate the PPAR pathway. These activities are associated with lower prevalence of thymic lymphomas and inhibition of CD8+ T-cell accumulation. Lymphomas derived from dimeric p53 mice show cooperating alterations in the PPAR pathway, further implicating a role for these activities in tumor suppression. Our data reveal novel functions for p53 dimers and support the exploration of PPAR agonists as therapies.
2023-03-01 | GSE220961 | GEO
Project description:Puri2010 - Mathematical Modeling for the
Pathogenesis of Alzheimer's Disease
Puri2010 - Mathematical Modeling for the Pathogenesis of
Alzheimer's Disease
Encoded non-curated model. Issues:
- Confusing replacement of
α16
when t = 3 years
- Confusing 4th rate equation
This model is described in the article:
Mathematical modeling for
the pathogenesis of Alzheimer's disease.
Puri IK, Li L.
PLoS ONE 2010; 5(12): e15176
Abstract:
Despite extensive research, the pathogenesis of
neurodegenerative Alzheimer's disease (AD) still eludes our
comprehension. This is largely due to complex and dynamic
cross-talks that occur among multiple cell types throughout the
aging process. We present a mathematical model that helps
define critical components of AD pathogenesis based on
differential rate equations that represent the known
cross-talks involving microglia, astroglia, neurons, and
amyloid-? (A?). We demonstrate that the inflammatory activation
of microglia serves as a key node for progressive
neurodegeneration. Our analysis reveals that targeting
microglia may hold potential promise in the prevention and
treatment of AD.
This model is hosted on
BioModels Database
and identified by:
MODEL1409240001.
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.
2015-04-15 | MODEL1409240001 | BioModels