PXD070615

PXD070615 is an original dataset announced via ProteomeXchange.

Title	Alzheimer’s Disease-Associated circPDE4B Triggers Translation Stress Pathways
Description	In the intricate landscape of Alzheimer’s disease (AD) pathology, circular RNAs(circRNA) are emerging as influential players, orchestrating crucial aspects of gene expression, synaptic plasticity, and neuronal function. In this study, we characterize the biological role of circPDE4B, a highly abundant circRNA that is markedly downregulated in AD across brain regions. Unlike most circRNAs, circPDE4B is expressed at substantially higher levels than its linear PDE4B transcript, suggesting a distinctive regulatory significance. Functional analyses in neuronal precursor cells revealed that circPDE4B reduction triggers a translational stress response, indicating its critical role in maintaining protein synthesis homeostasis. Immunoprecipitation identified several RNA-binding proteins associated with circPDE4B, among which the translation factor Gemin5 emerged as a key mediator of its effects on translation. Loss of circPDE4B also reduced mTOR levels and subsequently enhanced autophagic flux. Notably, circPDE4B downregulation was sufficient to mitigate tau pathology in a 3D assembloid model of tauopathy. We also identified a subset of AD-associated miRNAs interacting with circPDE4B, implicating additional layers of post-transcriptional regulation. Collectively, these findings define circPDE4B as a multifunctional regulator of neuronal homeostasis that integrates translational control, autophagic activity, and miRNA-mediated pathways, illuminating its potential involvement in the stress response and pathophysiology of AD
HostingRepository	PRIDE
AnnounceDate	2026-05-25
AnnouncementXML	Submission_2026-05-24_16:29:22.565.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sophie van der Spek
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-11 18:52:15	ID requested
⏵ 1	2026-05-24 16:29:23	announced

10.1002/alz.71436;

Puri S, van der Spek SJF, Lin M, Wang Z, Porter J, Hu J, Hu L, Rond, ó, n-Ortiz AN, Knyshov A, Libera JL, Counts SE, Lahiri DK, Tcw J, Emili A, Zhang X, Wolozin B, dependent translational stress response and autophagy to reduce MAPT pathology. Alzheimers Dement, 22(5):e71436(2026) [pubmed]

submitter keyword: Gemin5, Stress,circPDE4B, Translation, Alzheimer's Disease

Benjamin Wolozin
contact affiliation	Department of Anatomy and Neurobiolog; Department of Pharmacology, Physiology and Biophysics; Department of Neurology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, 02118, USA
contact email	bwolozin@bu.edu
lab head
Sophie van der Spek
contact affiliation	BU, Boston, USA
contact email	sophiejf@hotmail.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/2026/05/PXD070615

PRIDE project URI

• PRIDE
  1. PXD070615
     1. Label: PRIDE project
     2. Name: Alzheimer’s Disease-Associated circPDE4B Triggers Translation Stress Pathways