PXD064265

PXD064265 is an original dataset announced via ProteomeXchange.

Title	Ubiquitin-Proteasome System Dyeregulation in Alzheimer's Disease Impacts Protein Abundance.
Description	Alzheimer’s disease is a relentlessly progressive, fatal neurodegenerative disorder associated with widespread aberrant proteomic changes. The full extent of protein dysfunctions in AD and their impact on cellular physiology remains unknown. Here, we used plexDIA, a proteomic profiling approach that parallelizes the acquisition of samples and peptides, to characterize proteomic changes in AD. Using human dorsolateral prefrontal cortex tissue, we identified 281 differentially abundant proteins between AD and non-AD, including multiple AD-associated proteins, as well as many proteins with no known role in AD. By systematically analyzing cellular compartment-specific shifts in protein abundance, we identified an AD specific decrease in levels of the 20S proteasome, the catalytic core of the cell’s primary protein degradation pathway. Many proteasome substrate proteins were negatively correlated with 20S levels and increased in AD, suggesting reduced 20S levels lead to abnormal protein accumulation. By analyzing proteins increased in AD, we identify key properties of such proteins. Namely, they have highly specific subcellular localizations and fast degradation rates, they contain signal sequences that allow them to be targeted for proteasomal degradation, and they are targeted by quality control pathways that recognize mislocalized proteins. Furthermore, we identify coherent sets of ubiquitin system enzymes, proteins that mark substrates for proteasomal degradation, whose levels robustly discriminate AD from non ADsamples. One subset exhibited consistent increases in AD, while consistent decreases were observed in the other, revealing complex alterations in substrate targeting pathways. Taken together, our results suggest that decreased ubiquitin proteasome system capacity and impaired clearance of short-lived and mislocalized proteins contribute substantially to proteopathic burden in AD
HostingRepository	PRIDE
AnnounceDate	2025-05-27
AnnouncementXML	Submission_2025-05-27_13:03:24.636.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Corinna Friedrich
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-24 10:18:48	ID requested
⏵ 1	2025-05-27 13:03:25	announced

Dataset with its publication pending

submitter keyword: Alzheimer's disease,human

Nikolai Slavov
contact affiliation	Parallel Squared Technology Institute, Watertown, MA Department of bioengineering, Northeastern University, Boston, MA
contact email	nslavov@parallelsq.org
lab head
Corinna Friedrich
contact affiliation	Parallel Squared Technology Institute
contact email	cfriedrich@parallelsq.org
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/2025/05/PXD064265

PRIDE project URI

• PRIDE
  1. PXD064265
     1. Label: PRIDE project
     2. Name: Ubiquitin-Proteasome System Dyeregulation in Alzheimer's Disease Impacts Protein Abundance.