Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

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

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

DISEASE(S): Frontotemporal Dementia

SUBMITTER: Renren (Heidy) Chen

LAB HEAD: Dr Benjamin Ryskeldi-Falcon

PROVIDER: PXD043731 | Pride | 2023-08-25

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

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

TAF15 amyloid filaments in neurodegenerative disease

Project description:Frontotemporal dementia (FTD) is the most common form of dementia after Alzheimer's disease and results from frontotemporal lobar degeneration (FTLD). The pathological hallmarks of FTLD are neuronal inclusions of specific, abnormally assembled proteins1. In the majority of cases, the inclusions contain amyloid filament assemblies of TAR DNA-binding protein 43 (TDP-43) or tau, with distinct filament structures characterising different FTLD subtypes2,3. The presence, identities and structures of amyloid filaments in the remaining ~10% of FTLD cases are unknown, but are widely believed to be composed of the protein fused in sarcoma (FUS). As such, these cases are commonly referred to as FTLD-FUS. Here, we used cryogenic electron microscopy (cryo-EM) to determine the structures of amyloid filaments extracted from the prefrontal and temporal cortices of four individuals with FTLD-FUS. Unexpectedly, we found abundant amyloid filaments of the FUS homologue TATA-binding protein-associated factor 15 (TAF15), rather than of FUS itself. The filament fold is formed from residues 7 to 99 in the low-complexity domain (LCD) of TAF15 and was identical between individuals. The formation of TAF15 amyloid filaments with a characteristic fold in FTLD establishes TAF15 proteinopathy in neurodegenerative disease. Furthermore, we found TAF15 filaments with the same fold in the motor cortex and brainstem of two of the individuals, who also showed changes associated with amyotrophic lateral sclerosis (ALS), suggesting that TAF15 proteinopathy may underlie a disease spectrum of FTLD and ALS. The structure of TAF15 amyloid filaments provides a basis for the development of model systems of neurodegenerative disease, as well as for the design of diagnostic and therapeutic tools targeting TAF15 proteinopathy.

2023-12-07 | PXD044821 | Pride

smRNA-sequencing of human post-mortem brain tissue of the frontal lobe from patients with Frontotemporal Dementia and healthy controls

Project description:Understanding the molecular mechanisms underlying frontotemporal dementia (FTD) is essential for the development of successful therapies. Systematic studies on human post-mortem brain tissue of patients with genetic subtypes of FTD are currently lacking. The Risk and Modyfing Factors of Frontotemporal Dementia (RiMod-FTD) consortium therefore has generated multi-omics datasets for genetic subtypes of FTD to identify common and distinct molecular mechanisms disturbed in disease. This experiment contains data from smRNA-sequencing of human post-mortem brain tissue of the frontal lobe from patients with FTD caused by mutations in GRN, MAPT or C9orf72 and healthy controls.

2023-02-26 | E-MTAB-12731 | biostudies-arrayexpress

Mapping of TDP-43 ubiquitination and acetylation sites

Project description:TAR DNA binding protein of 43 kDa (TDP-43) forms aggregates in neurodegenerative diseases, particularly certain forms of frontotemporal dementia and amyotrophic lateral sclerosis. Pathological modifications of TDP-43 include proteolytic fragmentation, phosphorylation, and ubiquitinylation. In this study, we systematically mapped TDP-42 ubiquitination as well as acetylation sites.

2022-04-01 | PXD030170 | Pride

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

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

Gel-like inclusions of C-terminal fragments of TDP-43 sequester and inhibit proteasomes

Project description:TDP-43 inclusions enriched in C-terminal terminal fragments of ~25 kDa ("TDP-25") are associated with neurodegeneration in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here, we analyzed gain-of-function mechanisms of TDP-25 combining cryo-electron tomography, proteomics and functional assays. We show that TDP-25 inclusions are amorphous with gel-like properties. Inclusions sequester proteasomes adopting exclusively substrate-processing conformations. This leads to proteostasis impairment, further enhanced by pathogenic mutations. These findings bolster the importance of proteasome dysfunction in ALS/FTD.

2022-04-14 | PXD024358 | Pride

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

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

| PRJNA644618 | ENA

RNA-seq of human post-mortem brain tissue of the frontal lobe from patients with FTD and healthy controls

Project description:Understanding the molecular mechanisms underlying frontotemporal dementia (FTD) is essential for the development of successful therapies. Systematic studies on human post-mortem brain tissue of patients with genetic subtypes of FTD are currently lacking. The Risk and Modyfing Factors of Frontotemporal Dementia (RiMod-FTD) consortium therefore has generated multi-omics datasets for genetic subtypes of FTD to identify common and distinct molecular mechanisms disturbed in disease. This experiment contains data from RNA-sequencing of human post-mortem brain tissue of the frontal lobe from patients with FTD caused by mutations in GRN, MAPT or C9orf72 and healthy controls.

2023-02-17 | E-MTAB-12647 | biostudies-arrayexpress

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