PXD052770

PXD052770 is an original dataset announced via ProteomeXchange.

Title	Cognition-Associated Structural Changes Across the Neuroproteome in a Rodent Model of Aging are Correlated with Reduced Refolding Capacity ---- Cognition
Description	Cognitive decline in aging is a major issue, causing both personal and economic hardship in an increasingly aging society. There are several known individual misfolded proteins that cause issues with age, such as amyloid beta and alpha synuclein. However, many studies have found that the proteostasis network, which works to keep proteins properly folded, is impaired with age, suggesting that there may be more global protein structural changes. We used limited-proteolysis mass spectrometry (LiP-MS) to investigate protein structural changes proteome-wide in a rodent model of aging. We compared hippocampi from aged rodents with normal cognition (aged unimpaired, AU) to hippocampi from aged rodents with impaired cognition (aged impaired, AI). We identified several hundred proteins as Cognition-Associated Structural Changes (CASCs), which are structurally different between the AU and AI populations. We found correlations between these trends and those of protein refoldability, a separate measure of how well a protein can independently refold to its native state after complete denaturation. CASCs were enriched with nonrefoldable proteins. Potential confounding factors of our study such as LiP reproducibility and post-translational modifications were assessed. Searches for oxidation and phosphorylation did not yield significant differences between AU and AI samples within each hippocampal region. Our study overall suggests that neuronal protein structural changes are global in nature and are more often intrinsically nonrefoldable, which may partially explain their susceptibility to structural changes due to proteostasis network breakdown in age.
HostingRepository	PRIDE
AnnounceDate	2025-07-13
AnnouncementXML	Submission_2025-07-12_16:53:34.142.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Haley Tarbox
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-01 00:47:29	ID requested
⏵ 1	2025-07-12 16:53:34	announced

10.1126/SCIADV.ADT3778;

submitter keyword: brain, rat, protein structure,LiP-MS

Stephen David Fried
contact affiliation	Department of Chemistry, Johns Hopkins University, Baltimore, Maryland, United States
contact email	sdfried@jhu.edu
lab head
Haley Tarbox
contact affiliation	Johns Hopkins University
contact email	htarbox1@jhu.edu
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/2025/07/PXD052770

PRIDE project URI

• PRIDE
  1. PXD052770
     1. Label: PRIDE project
     2. Name: Cognition-Associated Structural Changes Across the Neuroproteome in a Rodent Model of Aging are Correlated with Reduced Refolding Capacity ---- Cognition