PXD057545

PXD057545 is an original dataset announced via ProteomeXchange.

Title	Chaperone-mediated autophagy sex-specifically regulates neuronal activity by remodeling the synaptic proteome
Description	Chaperone-mediated autophagy (CMA) declines in aging and neurodegenerative diseases. CMA loss in neurons leads to neurodegeneration and behavioral changes in mice, but the role of CMA in neuronal physiology is largely unknown. Here, we show that CMA deficiency causes neuronal hyperactivity, disrupted calcium homeostasis and abnormally increased presynaptic neurotransmitter release in females and elevated postsynaptic AMPA signaling in males. Comparative quantitative proteomics revealed sexual dimorphism in the synaptic proteins degraded by CMA, with preferential remodeling of the presynaptic proteome in females and the postsynaptic proteome in males. We propose that impaired lysosomal degradation of these synaptic proteins may contribute to hyperexcitability in aging and neurodegeneration. Accordingly, we demonstrate that pharmacological CMA activation in an Alzheimer’s disease mouse model normalizes synaptic protein levels and neurotransmission. These findings unveil a role for CMA in the regulation of neuronal excitability and highlight this pathway as a potential target for mitigating age-related decline in neuronal function.
HostingRepository	PRIDE
AnnounceDate	2025-09-05
AnnouncementXML	Submission_2025-09-04_16:17:32.021.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Simone Sidoli
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	2024-11-05 10:16:01	ID requested
⏵ 1	2025-09-04 16:17:32	announced

Dataset with its publication pending

submitter keyword: Aging

Alzheimer’s disease

autophagy

hyperexcitability

lysosomes

neurodegeneration

sexual dimorphism

synaptic plasticity

Simone Sidoli
contact affiliation	Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, United States
contact email	simone.sidoli@einsteinmed.edu
lab head
Simone Sidoli
contact affiliation	Albert Einstein College of Medicine
contact email	simone.sidoli@gmail.com
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/PXD057545

PRIDE project URI

• PRIDE
  1. PXD057545
     1. Label: PRIDE project
     2. Name: Chaperone-mediated autophagy sex-specifically regulates neuronal activity by remodeling the synaptic proteome