PXD057677

PXD057677 is an original dataset announced via ProteomeXchange.

Title	Label free -DDA nano-LC/MS/MS analysis of aggregates and total hippocampal proteome in an early AD mouse model following activation of chaperone-mediated autophagy
Description	Neurons are postmitotic cells that are highly sensitive to proteotoxic insults and reliant on tight protein quality control. Several forms of autophagy co-exist in neurons to maintain proteostasis. Defective autophagic pathways are one of the key hallmarks of the aging and neurodegenerative brains. Chaperone-mediated autophagy (CMA) declines in neurons in aging and neurodegenerative diseases including Alzheimer’s (AD) and Parkinson’s disease. CMA loss in neurons leads to protein aggregation, neuronal hyperactivity, neurodegeneration, and cognitive decline, all reminiscent of brain again. Conversely, pharmacological enhancement of CMA reduces pathological tau and β-amyloid accumulation, mitigates neuronal hyperactivity and seizure susceptibility and ameliorates cognitive decline in multiple tauopathy mouse models. The molecular mechanism underlying the beneficial role of CMA activation in AD is largely unknow. Furthermore, neuronal hyperactivity has recently been proposed as an early hallmark of AD. However, the mechanisms underlying early neuronal hyperactivity in AD are also not fully understood. To investigate these molecular mechanisms, we performed quantitative proteomics in an AD mouse model in early disease following CMA activation. The study analyzed total as well as aggregating proteome in hippocampus of triple-transgenic (x3TG) AD mice (expressing APPSwe, PS2N141I, and hTauP301L) following CMA activation with CA77.1 from 4-6 months of age. 5-6 samples per group were analyzed. Following bottom-up analysis, the enrichment analysis – GO, Ingenuity pathway analysis (IPA) and String analysis identified several pathways predicting aberrant synaptogenesis and increased activation of excitatory synaptic proteome including glutamate receptor signaling which was corrected by CMA activation. CMA activation also reverted the enrichment of synaptic proteins in the aggregates in early AD hippocampus which may restore their aggregation-driven loss of function.
HostingRepository	PRIDE
AnnounceDate	2025-09-04
AnnouncementXML	Submission_2025-09-04_07:52:31.284.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	ZOHAIB KHAN
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-08 11:26:31	ID requested
⏵ 1	2025-09-04 07:52:31	announced

Dataset with its publication pending

submitter keyword: Chaperone-mediated autophagy (CMA),Neurodegeneration

Laura Santambrogio
contact affiliation	Department of Radiation Oncology. Weill Cornell Medicine, New York
contact email	las4011@med.cornell.edu
lab head
ZOHAIB KHAN
contact affiliation	WEILL CORNELL MEDICINE
contact email	znk4001@med.cornell.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/2025/09/PXD057677

PRIDE project URI

• PRIDE
  1. PXD057677
     1. Label: PRIDE project
     2. Name: Label free -DDA nano-LC/MS/MS analysis of aggregates and total hippocampal proteome in an early AD mouse model following activation of chaperone-mediated autophagy