Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Reversing lysosome-mTORC1-ribosome axis dysregulations to mitigate C9FTD/ALS neurodegeneration [bulk RNA-Seq]

ABSTRACT: We report the application of buld RNA-seq in the mouse cortex with C9FTD/ALS neurodegeneration

ORGANISM(S): Mus musculus

PROVIDER: GSE206665 | GEO | 2023/06/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Reversing lysosome-mTORC1-ribosome axis dysregulations to mitigate C9FTD/ALS neurodegeneration [snRNA-Seq]

Project description:We report the application of snRNA-seq in the mouse cortex with C9FTD/ALS neurodegeneration

2023-06-30 | GSE206664 | GEO

Reversing lysosome-mTORC1-ribosome axis dysregulations to mitigate C9FTD/ALS neurodegeneration

Project description:Reversing lysosome-mTORC1-ribosome axis dysregulations to mitigate C9FTD/ALS neurodegeneration

| PRJNA851737 | ENA

Reversing lysosome-mTORC1-ribosome axis dysregulations to mitigate C9FTD/ALS neurodegeneration

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-06-30 | GSE206666 | GEO

Reversing lysosome-mTORC1-ribosome axis dysregulations to mitigate C9FTD/ALS neurodegeneration [snRNA-Seq]

Project description:Reversing lysosome-mTORC1-ribosome axis dysregulations to mitigate C9FTD/ALS neurodegeneration [snRNA-Seq]

| PRJNA851741 | ENA

Reversing lysosome-mTORC1-ribosome axis dysregulations to mitigate C9FTD/ALS neurodegeneration [bulk RNA-Seq]

Project description:Reversing lysosome-mTORC1-ribosome axis dysregulations to mitigate C9FTD/ALS neurodegeneration [bulk RNA-Seq]

| PRJNA851740 | ENA

Neuronal polyunsaturated fatty acids are protective in FTD/ALS

Project description:We report a conserved transcriptomic signature of reduced fatty acid and lipid metabolism gene expression in human post-mortem ALS spinal cord and a Drosophila model of the most common genetic cause of FTD/ALS, a repeat expansion in C9orf72. To investigate lipid alterations, we performed lipidomics on C9FTD/ALS iPSC-neurons and post-mortem FTLD brain tissue. This revealed a common and specific reduction in phospholipid species containing polyunsaturated fatty acids (PUFAs). To determine whether this PUFA deficit contributes to neurodegeneration, we fed C9FTD/ALS flies PUFAs, which yielded a modest increase in survival. However, increasing PUFA levels specifically in neurons of the C9orf72 flies, by overexpressing fatty acid desaturase enzymes, led to a substantial extension of lifespan. Neuronal overexpression of fatty acid desaturases also suppressed stressor induced neuronal death in C9FTD/ALS patient iPSC-neurons. These data implicate neuronal fatty acid saturation in the pathogenesis of FTD/ALS and suggest that interventions to increase PUFA levels specifically within neurons will be beneficial.

2024-11-15 | GSE255099 | GEO

Reduction of Nemo-like kinase increases lysosome biogenesis and ameliorates TDP-43-related neurodegeneration

Project description:Protein aggregation is a hallmark of many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). Although mutations in TARDBP, encoding TDP-43, account for less than 1% of all ALS cases, TDP-43-positive aggregates are present in nearly all ALS patients, including patients with sporadic ALS (sALS) or carrying other familial ALS (fALS)-causing mutations. Interestingly, TDP-43 inclusions are also present in subsets of patients with frontotemporal dementia, Alzheimer’s disease, and Parkinson’s disease; therefore, methods of activating intracellular protein quality control machinery capable of clearing toxic cytoplasmic TDP-43 species may alleviate disease-related phenotypes. Here, we identify a novel function of Nemo-like kinase (Nlk) as a negative regulator of lysosome biogenesis. Genetic or pharmacological reduction of Nlk increased lysosome formation and improved clearance of aggregated TDP-43. Furthermore, Nlk reduction ameliorated pathological, behavioral, and lifespan deficits in two distinct mouse models of TDP-43 proteinopathy. Because many toxic proteins can be cleared along the autophagy-lysosome axis, targeted reduction of Nlk represents a potential approach to therapy development for multiple neurodegenerative disorders.

2023-06-24 | GSE235312 | GEO

SYF2 Suppression Mitigates Neurodegeneration in Models of Diverse Forms of ALS

Project description:RNA sequencing analysis of human induced motor neurons generated from a C9ORF72 ALS patient line and its isogenic control, treated with siRNA targetting SYF2. The goal of this study is to evaluate the process of SYF2 suppression in rescuing ALS motor neuron degeneration.

2022-11-23 | GSE218079 | GEO

UBQLN2 Governs Lipid Metabolism Linked to Neurodegeneration in ALS/FTD

Project description:Missense mutations in UBQLN2, a protein quality control factor, are associated with neurodegenerative diseases amyotrophic lateral sclerosis (ALS) overlapping with frontotemporal dementia (FTD). The mechanisms by which these mutations lead to neurodegeneration are not fully understood. Here we describe a critical role for UBQLN2 in regulating cellular lipid metabolism, which is crucial for cell survival under nutrient stress. The stress dependent regulation of lipid metabolism by UBQLN2 is mediated by ILVBL, a UBQLN2 substrate and a key enzyme in lipid turnover. The function of UBQLN2 in promoting ILVBL degradation and maintaining intracellular lipids was compromised by ALS/FTD-linked mutations in UBQLN2. As a result of the lipid dysregulation, synaptic vesicles were deficient and neuronal death was exacerbated in mutant UBQLN2 transgenic mice or human iPSCs derived motor neurons and cortical organoids. Replenishing lipids or restoring UBQLN2 function could reverse the deficits in the UBQLN2 mutant neurons under nutrient stress. Our study reveals UBQLN2 essential role in lipid metabolism and suggests metabolic imbalance underlying ALS/FTD and related neurodegenerative conditions.

2023-12-27 | MSV000093732 | MassIVE

RNA sequencing of human fibroblasts after SUPT4H1 siRNA treatment

Project description:Asses the transcriptome-wide changes associated with depletion of transcription elongation factor, SUPT4H1, in human fibroblasts. An expanded hexanucleotide repeat in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9FTD/ALS). Therapeutics (e.g., antisense oligonucleotides) are being developed to target RNAs containing the expanded repeat sequence (GGGGCC); however, this approach is complicated by the presence of antisense strand transcription of expanded GGCCCC repeats. We found that targeting the transcription elongation factor, Spt4, selectively decreased production of both sense and antisense expanded transcripts, as well as their translated dipeptide repeat (DPR) products, and also mitigated degeneration in animal models. Inhibition of SUPT4H1, the human ortholog of Spt4, similarly decreased production of sense and antisense RNA foci as well as DPR proteins in c9ALS patient fibroblasts and neurons from patient-derived induced pluripotent stem cells, consistent with our finding that cerebellar DPR protein levels correlate with SUPT4H1 expression in c9FTD/ALS patients. Therapeutic targeting of a single factor to eliminate pathological features of c9FTD/ALS offers advantages over approaches that require targeting sense and antisense repeats separately.

2016-09-09 | GSE83484 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data