PXD067550

PXD067550 is an original dataset announced via ProteomeXchange.

Title	HSPA4 restrains transferrin in dopaminergic neurons to attenuate ferroptosis in a Parkinson’s disease model
Description	Heat shock protein A4 (HSPA4) is a molecular chaperone belonging to the heat shock protein 70 (HSP70) family. This study aims to investigate the antiferroptotic effects of HSPA4 in a Parkinson’s disease (PD) model and explore the underlying mechanisms. Here we show that HSPA4 overexpression reduces ferroptosis in erastin-treated SH-SY5Y cells and primary dopaminergic neurons, while HSPA4 knockdown exacerbates ferroptosis. In MPTP-induced PD model mice, HSPA4 rectifies behavioral defects, prevents the loss of dopaminergic neurons, and alleviates ferroptosis. Mechanistically, HSPA4 interacts with transferrin in the cytoplasm and inhibits its export from the cell. Consequently, extracellular iron cannot be transported into cells due to a lack of transferrin, thereby attenuating ferroptosis in dopaminergic neurons and slowing PD progression. By restraining transferrin in dopaminergic neurons, HSPA4 reduces ferroptosis and alleviates parkinsonism in a PD mouse model. Therefore, HSPA4 might present a potential therapeutic target for the development of PD treatments.
HostingRepository	PRIDE
AnnounceDate	2025-10-20
AnnouncementXML	Submission_2025-10-19_16:06:50.873.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Qianqian JU
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-21 05:12:38	ID requested
⏵ 1	2025-10-19 16:06:51	announced

10.1038/s42003-025-08854-7;

Gao T, Wei H, Ju Q, Lin Y, Yin X, Liu X, Shen J, Ji Q, Sun C, Shen L, HSPA4 restrains transferrin in dopaminergic neurons to attenuate ferroptosis in a Parkinson's disease model. Commun Biol, 8(1):1453(2025) [pubmed]

submitter keyword: Dopaminergic neurons,HSPA4, Parkinson’s disease, Ferroptosis, Transferrin

Cheng Sun
contact affiliation	Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering of Life Science, Nantong University, Nantong, China.
contact email	suncheng1975@ntu.edu.cn
lab head
Qianqian JU
contact affiliation	nantong university
contact email	907482591@qq.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/2025/10/PXD067550

PRIDE project URI

• PRIDE
  1. PXD067550
     1. Label: PRIDE project
     2. Name: HSPA4 restrains transferrin in dopaminergic neurons to attenuate ferroptosis in a Parkinson’s disease model