Rattus norvegicus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA112959 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Primary neuron model of Huntington's Disease. 2 treatment groups: A) Infected 4 weeks prior with TRE-Htt-N853-18Q-expressing recombinant lentivirus, B) Infected 4 weeks prior with TRE-Htt-N853-82Q-expressing recombinant lentivirus Experiment Overall Design: Primary neurons samples infected with TRE-Htt-N853-18Q or -82Q.
2008-10-25 | E-GEOD-12481 | biostudies-arrayexpress
Project description:Primary neuron model of Huntington's Disease. 2 treatment groups: A) Infected 4 weeks prior with TRE-Htt-N853-18Q-expressing recombinant lentivirus, B) Infected 4 weeks prior with TRE-Htt-N853-82Q-expressing recombinant lentivirus Keywords: gene expression study
2008-09-01 | GSE12481 | GEO
Project description:Transcription profiling by array of striatum from a mouse model of Huntington's disease
2014-10-10 | E-GEOD-18551 | ExpressionAtlas
Project description:Depletion of p62 reduces nuclear inclusions and paradoxically ameliorates disease phenotypes in Huntington's model mice
2014-10-27 | E-GEOD-62210 | ExpressionAtlas
Project description:Huntington's disease (HD) is characterized by the aggregation of polyglutamine-expanded huntingtin (HTT), proceeding from soluble oligomers to end-stage inclusions. The molecular mechanisms of how protein aggregation leads to neuronal dysfunction are not well understood. We employed mass spectrometry-based quantitative proteomics to dissect spatiotemporal mechanisms of neurodegeneration using the R6/2 mouse model of HD. We show that extensive remodeling of the soluble brain proteome correlates with changes in insoluble aggregate formation during disease progression. In-depth characterization of HTT inclusion bodies uncovered an unprecedented complexity of several hundred proteins. Sequestration to inclusions was dependent on protein expression levels and the presence of aggregation-prone amino acid sequence features, such as low-complexity regions or coiled-coil domains. Overexpression of several sequestered proteins ameliorated HTT toxicity and modified the aggregation behavior in an in vitro model of HD. Our study provides a comprehensive and spatiotemporally-resolved proteome resource of HD progression, indicating that widespread loss of protein function contributes to aggregate-mediated toxicity.
2017-11-24 | PXD004973 | Pride
Project description:Transcriptional changes are an early feature of Huntington's disease (HD). We profiled genome-wide interaction sites for the huntingtin protein (HTT) using ChIP-sequencing from mouse striatal tissue at 4 months of age. We include replicate samples from CAG-expanded murine Htt (heterozygous Q111/+) and wildtype littermate controls.
2018-12-01 | GSE102750 | GEO
Project description:We used microarrays to investigate whether transcriptional dysregulation in hypothalamus is caused by expression of the huntingtin (HTT) protein We used two different Huntington's disease mouse models: BACHD mice with ubiquitous full-length mutant HTT expression (97 CAG repeats) and wild-type mice with targeted bilateral injections of wild-type or mutant HTT (853 amino acids length, wild-type HTT: 18 CAG repeats, mutant HTT: 79 CAG repeats) in hypothalamus.
2022-10-18 | GSE215217 | GEO
Project description:Despite growing descriptions of wild-type Huntingtin's (wt-HTT) roles in both adult brain function and, more recently, development, several clinical trials are exploring HTT-lowering approaches that target both wt-HTT and the mutant isoforms (mut-HTT) responsible for Huntington's disease (HD). This non-selective targeting is based on the autosomal dominant inheritance of HD, supporting the idea that mutant HTT exerts its harmful effects through a toxic gain-of-function or a dominant-negative mechanism. However, the precise amount of wt-HTT needed for healthy neurons in adults and during development remains unclear. In this study, we address this question by examining how wt-HTT loss affects human neuronal network formation, synaptic maturation, and homeostasis in vitro. Our findings establish a role of wt-HTT in the maturation of dendritic arborization and the acquisition of network-wide synchronized activity by human cortical neuronal networks modeled in vitro. Interestingly, the network synchronization defects only became apparent when more than two-thirds of the wt-HTT protein was depleted. Our study underscores the critical need to precisely understand wt-HTT's role in neuronal health. It also emphasizes the potential risks of excessive wt-HTT loss associated with non-selective therapeutic approaches targeting both wt and mutant HTT isoforms in HD patients.
2025-03-25 | PXD053150 | Pride
Project description:In Huntington's disease (HD), polyglutamine expansions in the huntingtin (Htt) protein cause subtle changes in cellular functions that, over-time, lead to neurodegeneration and death. Studies have indicated that activation of the heat shock response can reduce many of the effects of mutant Htt in disease models, suggesting that the heat shock response is impaired in the disease. To understand the basis for this impairment, we have used genome-wide chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-Seq) to examine the effects of mutant Htt on the master regulator of the heat shock response, HSF1. We find that, under normal conditions, HSF1 function is highly similar in cells carrying either wild-type or mutant Htt. However, polyQ-expanded Htt severely blunts the HSF1-mediated stress response. Surprisingly, we find that the HSF1 targets most affected upon stress are not directly associated with proteostasis, but with cytoskeletal binding, focal adhesion and GTPase activity. Our data raise the intriguing hypothesis that the accumulated damage from life-long impairment in these stress responses may contribute significantly to the etiology of Huntington's disease. Affymetrix MG430 2.0 expression levels of wild-type (STHdhQ7/Q7) and mutant (STHdhQ111/Q111) striatal cells under growth condition (33 C) and upon heat shock (42 C for six hours)
2012-06-18 | E-GEOD-38001 | biostudies-arrayexpress