Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Truncated stathmin-2 is a marker of TDP-43 pathology in frontotemporal dementia

ABSTRACT: Truncated stathmin-2 is a marker of TDP-43 pathology in frontotemporal dementia

PROVIDER: PRJNA644618 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR12165800_1.fastq.gz	Fastqsanger.gz
	SRR12165800_2.fastq.gz	Fastqsanger.gz
	SRR12165900_1.fastq.gz	Fastqsanger.gz
	SRR12165900_2.fastq.gz	Fastqsanger.gz
	SRR12166000_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 4512

Similar Datasets

Truncated stathmin-2 is a marker of TDP-43 pathology in frontotemporal dementia

Project description:No treatment for frontotemporal dementia (FTD), the second most common type of early-onset dementia, is available, but therapeutics are being investigated to target the 2 main proteins associated with FTD pathological subtypes: TDP-43 (FTLD-TDP) and tau (FTLD-tau). Testing potential therapies in clinical trials is hampered by our inability to distinguish between patients with FTLD-TDP and FTLD-tau. Therefore, we evaluated truncated stathmin-2 (STMN2) as a proxy of TDP-43 pathology, given the reports that TDP-43 dysfunction causes truncated STMN2 accumulation. Truncated STMN2 accumulated in human induced pluripotent stem cell–derived neurons depleted of TDP-43, but not in those with pathogenic TARDBP mutations in the absence of TDP-43 aggregation or loss of nuclear protein. In RNA-Seq analyses of human brain samples from the NYGC ALS cohort, truncated STMN2 RNA was confined to tissues and disease subtypes marked by TDP-43 inclusions. Last, we validated that truncated STMN2 RNA was elevated in the frontal cortex of a cohort of patients with FTLD-TDP but not in controls or patients with progressive supranuclear palsy, a type of FTLD-tau. Further, in patients with FTLD-TDP, we observed significant associations of truncated STMN2 RNA with phosphorylated TDP-43 levels and an earlier age of disease onset. Overall, our data uncovered truncated STMN2 as a marker for TDP-43 dysfunction in FTD.

2020-10-20 | GSE153960 | GEO

Premature polyadenylation-mediated loss of stathmin-2 is a hallmark of TDP-43-dependent neurodegeneration

Project description:Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are associated with loss of nuclear TDP-43. Here we identify that TDP-43 regulates expression of the neuronal growth-associated factor stathmin-2. Lowered TDP-43 levels, which reduce its binding to sites within the first intron of stathmin-2 pre-mRNA, uncover a cryptic polyadenylation site whose utilization produces a truncated, non-functional mRNA. Reduced stathmin-2 expression is found in neurons trans-differentiated from patient fibroblasts expressing an ALS-causing TDP-43 mutation, in motor cortex and spinal motor neurons from sporadic ALS patients and familial ALS patients with expansion in C9orf72, and in induced pluripotent stem cell (iPSC)-derived motor neurons depleted of TDP-43. Remarkably, while reduction in TDP-43 is shown to inhibit axonal regeneration of iPSC-derived motor neurons, rescue of stathmin-2 expression restores axonal regenerative capacity. Thus, premature polyadenylation-mediated reduction in stathmin-2 is a hallmark of ALS/FTD that functionally links reduced nuclear TDP-43 function to enhanced neuronal vulnerability.

2019-01-01 | GSE122069 | GEO

Whole genome sequencing consortium on frontotemporal dementia with underlying TDP-43 pathology

Project description:Whole genome sequencing consortium on frontotemporal dementia with underlying TDP-43 pathology

| PRJNA976483 | ENA

Whole genome sequencing consortium on frontotemporal dementia with underlying TDP-43 pathology

Project description:Whole genome sequencing consortium on frontotemporal dementia with underlying TDP-43 pathology

| PRJNA976484 | ENA

TDP-43 forms amyloid filaments with a distinct fold in type A FTLD-TDP

Project description:TDP-43, amyloid, filament, fibril, protein aggregation, neurodegenerative disease, neurodegeneration, dementia, frontotemporal dementia, frontotemporal lobar degeneration, citrullination, methylation, brain

2023-08-25 | PXD040102 | Pride

TDP-43 forms amyloid filaments with a distinct fold in type A FTLD-TDP

2023-08-25 | PXD043731 | Pride

Truncated stathmin-2 is a marker of TDP-43 pathology in frontotemporal dementia.

Project description:No treatment for frontotemporal dementia (FTD), the second most common type of early-onset dementia, is available, but therapeutics are being investigated to target the 2 main proteins associated with FTD pathological subtypes: TDP-43 (FTLD-TDP) and tau (FTLD-tau). Testing potential therapies in clinical trials is hampered by our inability to distinguish between patients with FTLD-TDP and FTLD-tau. Therefore, we evaluated truncated stathmin-2 (STMN2) as a proxy of TDP-43 pathology, given the reports that TDP-43 dysfunction causes truncated STMN2 accumulation. Truncated STMN2 accumulated in human induced pluripotent stem cell-derived neurons depleted of TDP-43, but not in those with pathogenic TARDBP mutations in the absence of TDP-43 aggregation or loss of nuclear protein. In RNA-Seq analyses of human brain samples from the NYGC ALS cohort, truncated STMN2 RNA was confined to tissues and disease subtypes marked by TDP-43 inclusions. Last, we validated that truncated STMN2 RNA was elevated in the frontal cortex of a cohort of patients with FTLD-TDP but not in controls or patients with progressive supranuclear palsy, a type of FTLD-tau. Further, in patients with FTLD-TDP, we observed significant associations of truncated STMN2 RNA with phosphorylated TDP-43 levels and an earlier age of disease onset. Overall, our data uncovered truncated STMN2 as a marker for TDP-43 dysfunction in FTD.

| S-EPMC7598060 | biostudies-literature

Genome-wide DNA methylation analysis identifies epigenetic differences in Alzheimer’s disease and frontotemporal dementia in brain tissue and lymphoblastoid cell lines

Project description:We have performed methylation microarray analysis of two types of dementia, Alzheimer's disease (AD) and frontotemporal dementia (FTD), using two kind of samples, frozen brain tissue and lymphoblastoid cell lines.

2024-01-01 | E-MTAB-11975 | biostudies-arrayexpress

A role for astrocytic miR-129-5p in Frontotemporal Dementia

Project description:Frontotemporal dementia is a debilitating neurodegenerative disorder characterized by frontal and temporal lobe degeneration, resulting in behavioral changes, language difficulties, and cognitive decline. In this study, smallRNA sequencing was conducted on postmortem brain tissues obtained from FTD patients with GRN, MAPT, or C9ORF mutations, focusing on the frontal and temporal lobes. Our analysis identified miR-129-5p as consistently deregulated across all mutation conditions and brain regions. Functional investigations revealed a novel role of miR-129-5p in astrocytes, where its loss led to neuroinflammation and impaired neuronal support functions, including glutamate uptake. Depletion of miR-129-5p in astrocytes resulted in the loss of neuronal spines and altered neuronal network activity. These findings highlight miR-129-5p as a potential therapeutic target in neurodegenerative diseases and also sheds light on the role of astrocytes in Frontotemporal dementia pathogenesis.

2025-04-17 | GSE262895 | GEO

LSD1 inhibition induces neurodegeneration and provides a common link to Alzheimer's disease and Frontotemporal dementia

Project description:Alzheimer’s disease (AD) and Frontotemporal dementia (FTD) are the two most common forms of dementia that occur during aging. Both AD and FTD are associated with the pathological aggregation of proteins. Nevertheless, it remains unclear how these protein aggregates lead to neuronal cell death in these dementias. Here we show that the histone demethylase LSD1 is mislocalized with cytoplasmic aggregates in human cases of AD and FTD. In addition, loss of LSD1 systemically in adult mice is sufficient to recapitulate many aspects of these diseases. From these data, we propose that the aggregation of Tau and TDP-43 lead to neuronal cell death in AD and FTD by interfering with the continuous requirement for LSD1 to repress inappropriate transcription. Furthermore, we observe the inappropriate reactivation of stem cell loci in the hippocampal neurons of LSD1 mutant mice. This suggests that LSD1 may function to maintain the fate of differentiated neurons by repressing stem cell transcription.

2017-05-13 | GSE98875 | 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