PXD042382-2

PXD042382 is an original dataset announced via ProteomeXchange.

Title	A transient protein folding response targets aggregation in the early phase of TDP-43-mediated disease
Description	Understanding the mechanisms that drive TDP-43 pathology is integral to combating amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Here we generated a longitudinal quantitative proteomic map of the cortex from the cytoplasmic TDP-43 rNLS8 mouse model of ALS and FTLD and developed a complementary open-access webtool, TDP-map (https://shiny.rcc.uq.edu.au/TDP-map/). We identified distinct protein subsets enriched for diverse biological pathways with temporal alterations in protein abundance, including increases in protein folding factors prior to disease onset. This included increased levels of DnaJ homolog subfamily B member 5, DNAJB5, which also co-localized with TDP-43 pathology in diseased human motor cortex. DNAJB5 over-expression decreased TDP-43 aggregation in cell and cortical neuron cultures, and knockout of Dnajb5 exacerbated motor impairments caused by AAV-mediated cytoplasmic TDP-43 expression in mice. Together, these findings reveal molecular mechanisms at distinct stages of ALS and FTLD progression and suggest that protein folding factors could be protective in disease.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:28:09.331.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rebecca San Gil
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-21 23:03:05	ID requested
1	2024-01-30 20:40:49	announced
⏵ 2	2024-10-22 06:28:09	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: FTLD,Longitudinal, ALS, cortex, mouse, proteinopathy, motor neuron disease, MND, TDP-43, LC-MS/MS, tandem mass tagging, amyotrophic lateral sclerosis, frontotemporal dementia, FTD, frontotemporal lobar degeneration

Adam K.
contact affiliation	Neurodegeneration Pathobiology Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia
contact email	adam.walker@uq.edu.au
lab head
Rebecca San Gil
contact affiliation	The University of Queensland
contact email	r.sangil@uq.edu.au
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/01/PXD042382

PRIDE project URI

• PRIDE
  1. PXD042382
     1. Label: PRIDE project
     2. Name: A transient protein folding response targets aggregation in the early phase of TDP-43-mediated disease