Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA380229 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5368400.fastq.gz | Fastqsanger.gz | |||
| SRR5368410.fastq.gz | Fastqsanger.gz | |||
| SRR5368401.fastq.gz | Fastqsanger.gz | |||
| SRR5368411.fastq.gz | Fastqsanger.gz | |||
| SRR5368402.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 16 |
Similar Datasets
Project description:Elevated alpha-synuclein (SNCA) gene expression is associated with transcriptional deregulation and increased risk of Parkinson’s disease, which may be partially ameliorated by environmental enrichment. At the molecular level, emerging evidence indicates that excess alpha-synuclein protein (aSyn) impacts the epigenome through direct and/or indirect mechanisms. However, the extents to which both aSyn and the environment converge at the epigenome and whether epigenetic alterations underpin the preventive effects of environmental factors on transcription remain to be elucidated. Here, we profiled five DNA and histone modifications in the hippocampus of wild-type and transgenic mice overexpressing human SNCA. Mice of each genotype were housed under either standard conditions or in an enriched environment (EE) for 12 months. SNCA overexpression induced similar hippocampal DNA hydroxymethylation and H3K27 acetylation changes in both environments, and was associated with environment-dependent changes to H3K4 methylation. These H3K4 methylation changes included loci where the EE ameliorated the impacts of the transgene as well as loci resistant to the effects of environmental enrichment in transgenic mice. In addition, select H3K4 monomethylation alterations were associated with changes in mRNA expression. Our results suggested an environment-dependent impact of excess aSyn on some functionally relevant parts of the epigenome, and will ultimately enhance our understanding of the molecular etiology of Parkinson’s disease and other synucleinopathies.
2023-04-08 | GSE228961 | GEO
Project description:Global transcriptional analysis of the brain of multiple system atrophy model mice after synuclein induction by tamoxifen. Multiple system atrophy (MSA) is pathologically characterized by accumulation of phosphorylated α-synuclein in the oligodendrocytes. The pathophisiological mechinism under the early staige of disease pregression has been unknown. To clarify molecular alteration just after α-synuclein overexpression in the oligodendrocytes, we performed whole transcriptome analysis of the brain obtained from MSA model mice and control at 10 days after α-synuclein induction.
2021-06-01 | GSE129531 | GEO
Project description:A53T-α-synuclein overexpression mouse model signaling and striatal synaptic plasticity
| PRJNA125303 | ENA
Project description:Parkinson’s disease is characterized by the aggregation of the presynaptic protein α-synuclein and its deposition into pathologic Lewy bodies. While extensive research has been carried out on mediators of α-synuclein aggregation, molecular facilitators of α-synuclein disaggregation are still generally unknown. We investigated the role of molecular chaperones in both preventing and disaggregating α-synuclein oligomers and fibrils, with a focus on the mammalian disaggregase complex. Here, we show that overexpression of the chaperone Hsp110 is sufficient to reduce α-synuclein aggregation in a mammalian cell culture model. Additionally, we demonstrate that Hsp110 effectively mitigates α-synuclein pathology in vivo through the characterization of transgenic Hsp110 and double transgenic α-synuclein/Hsp110 mouse models. Unbiased analysis of the synaptic proteome of these mice revealed that overexpression of Hsp110 can override the protein changes driven by the α-synuclein transgene. Furthermore, overexpression of Hsp110 is sufficient to prevent endogenous α-synuclein templating and spread following injection of aggregated α-synuclein seeds into brain, supporting a role for Hsp110 in the prevention and/or disaggregation of α-synuclein pathology.
2020-05-26 | PXD016015 | Pride
Project description:Although Parkinson’s disease (PD) is one of the most rapidly growing neurological disorders, interindividual differences in PD etiology related to genetics are not fully understood. Here, we demonstrate genome-wide DNA methylation and hydroxymethylation alterations associated with overexpression of two PD-linked alpha-synuclein variants (wild type and A30P) in LUHMES cells differentiated to dopaminergic neurons. Alpha-synuclein altered DNA methylation at thousands of CpGs and DNA hydroxymethylation at hundreds of CpGs in both genotypes, and primarily at locomotor and glutamate signaling pathway genes. In some cases, epigenetic changes were associated with transcription. SMITE network analysis incorporating H3K4me1 ChIP-seq to score DNA methylation and hydroxymethylation changes across promoters, enhancers, and gene bodies confirmed epigenetic and transcriptional deregulation of glutamate signaling modules in both genotypes. Our results identify distinct and shared impacts of alpha-synuclein variants on the epigenome, and associate alpha-synuclein in the epigenetic etiology of PD.
2021-08-02 | GSE181126 | GEO
Project description:Ouzounoglou2014 - Modeling of alpha-synuclein
effects on neuronal homeostasis
This model is described in the article:
In silico modeling of the
effects of alpha-synuclein oligomerization on dopaminergic
neuronal homeostasis.
Ouzounoglou E, Kalamatianos D,
Emmanouilidou E, Xilouri M, Stefanis L, Vekrellis K, Manolakos
ES.
BMC Syst Biol 2014; 8: 54
Abstract:
BACKGROUND: Alpha-synuclein (ASYN) is central in Parkinson's
disease (PD) pathogenesis. Converging pieces of evidence
suggest that the levels of ASYN expression play a critical role
in both familial and sporadic Parkinson's disease. ASYN fibrils
are the main component of inclusions called Lewy Bodies (LBs)
which are found mainly in the surviving neurons of the
substantia nigra. Despite the accumulated knowledge regarding
the involvement of ASYN in molecular mechanisms underlying the
development of PD, there is much information missing which
prevents understanding the causes of the disease and how to
stop its progression. RESULTS: Using a Systems Biology
approach, we develop a biomolecular reactions model that
describes the intracellular ASYN dynamics in relation to
overexpression, post-translational modification,
oligomerization and degradation of the protein. Especially for
the proteolysis of ASYN, the model takes into account the
biological knowledge regarding the contribution of Chaperone
Mediated Autophagy (CMA), macro-autophagic and proteasome
pathways in the protein's degradation. Importantly, inhibitory
phenomena, caused by ASYN, concerning CMA (more specifically
the lysosomal-associated membrane protein 2a, abbreviated as
Lamp2a receptor, which is the rate limiting step of CMA) and
the proteasome are carefully modeled. The model is validated by
simulation studies of known experimental overexpression data
from SH-SY5Y cells and the unknown model parameters are
estimated either computationally or by experimental fitting.
The calibrated model is then tested under three hypothetical
intervention scenarios and in all cases predicts increased cell
viability that agrees with experimental evidence. The biomodel
has been annotated and is made available in SBML format.
CONCLUSIONS: The mathematical model presented here successfully
simulates the dynamic phenomena of ASYN overexpression and
oligomerization and predicts the biological system's behavior
in a number of scenarios not used for model calibration. It
allows, for the first time, to qualitatively estimate the
protein levels that are capable of deregulating proteolytic
homeostasis. In addition, it can help form new hypotheses for
intervention that could be tested experimentally.
Note: The model contains reactions of species located in different compartments. If the model is applied using volume sizes unequal to one, an extension of the model might be reasonable to guarantee mass conservation.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000559.
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 | BIOMD0000000559 | BioModels
Project description:Neuroinflammation and accumulation of alphα-synuclein (α-syn) are core features of Parkinson disease (PD). We found that α-syn-induced neuroinflammation is driven by antigen presentation from CNS resident macrophages. A subset of these, border-associated macrophages (BAMs), expand and express genes and proteins necessary for immune cell recruitment, infiltration, and antigen presentation, whereas depletion of BAMs prevents neuroinflammation and neurodegeneration. These results point to a critical role for BAMs in initiating PD pathogenesis.
2021-06-20 | GSE178498 | GEO
Project description:The goal of this study is to compare gene expression differences between WT and tPA KO mice 4 weeks after overexpression of human alpha-synuclein in the substantia nigra
2022-03-28 | E-MTAB-11567 | biostudies-arrayexpress
Project description:LUHMES cells share many characteritics with human dopamingeric neurons in the substantia nigra, the cells whose demise is responsible for the motor symptoms in Parkinson’s disease (PD). LUHMES cells can therefore be used bona fide as a model to study pathophysiological processes involved in PD. Previously, we showed that LUHMES cell degenerate after six days upon overexpression of wild type alpha-synuclein. In the present study we performed a transcriptome and proteome expression analysis in alpha-synuclein-overexpressing cells and GFP-expressing control cells in order to identify genes and proteins that are differentially regulated upon overexpression of alpha-synuclein. The analysis was performed four days after the initiation of alpha-synuclein or GFP overexpression, before the cells died in order to identify processes that preceded cell death.
2022-05-19 | PXD028322 | Pride
Project description:A major barrier to research on Parkinson’s disease (PD) is inaccessibility of diseased tissue for study. One solution is to derive induced pluripotent stem cells (iPSCs) from patients with PD and differentiate them into neurons affected by disease. We created an iPSC model of PD caused by triplication of SNCA encoding α-synuclein. α-Synuclein dysfunction is common to all forms of PD, and SNCA triplication leads to fully penetrant familial PD with accelerated pathogenesis. After differentiation of iPSCs into neurons enriched for midbrain dopaminergic subtypes, those from the patient contain double α-synuclein protein compared to those from an unaffected relative, precisely recapitulating the cause of PD in these individuals. A measurable biomarker makes this model ideal for drug screening for compounds that reduce levels of α-synuclein, and for mechanistic experiments to study PD pathogenesis. This gene expression microarray study was carried out as part of the validation process for demonstrating that the generated iPSC lines are pluripotent. 5 samples were analysed: two clonal iPSC lines from each of two genotypes (four in total; AST denoting alpha-synuclein triplication and NAS denoting normal alpha-synuclein), a human embryonic stem cell line (SHEF4). All cultured in self-renewal conditions, mTeSR1
2011-09-14 | E-GEOD-30792 | biostudies-arrayexpress