PXD061887

PXD061887 is an original dataset announced via ProteomeXchange.

Title	Casein kinase 1δ induces the formation of GVB-positive neurons that are resilient to tau-induced impairment of protein synthesis
Description	The progressive intraneuronal accumulation of protein aggregates is central in the pathogenesis of several neurodegenerative diseases. Therefore, molecular pathways that mediate neuronal resilience to tau pathology present interesting targets for therapeutic intervention. To this end we investigated the mechanism and functional implications of the formation of granulovacuolar degeneration bodies (GVBs), neuron-specific lysosomal structures that form in response to pathological tau assemblies. In the present work, we show that intraneuronal tau pathology progressively induces the formation of GVB+ neurons. We demonstrate that CK1δ activity is a rate limiting step in the formation of GVB+ neurons that requires the autophagic machinery. The GVB neuronal state confers protection against tau pathology: GVB+ neurons have structural adaptations in lysosomal and ribosomal content to become resilient to tau-induced protein synthesis impairment. Moreover, GVB+ neurons are functionally resilient to tau-induced neurodegeneration and impairment of LTP-regulated protein synthesis. Altogether our results have identified CK1δ as a key regulator of a protective neuron-specific proteostatic response to tau pathology.
HostingRepository	PRIDE
AnnounceDate	2026-03-09
AnnouncementXML	Submission_2026-03-08_17:17:39.181.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Debora Pita Illobre
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	S-carboxamidoethyl-L-cysteine
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-16 03:22:26	ID requested
⏵ 1	2026-03-08 17:17:40	announced

10.1126/sciadv.aea8940;

Smits JFM, Ligthart TW, Jorge-Oliva M, Middelhoff S, Schipper F, Pita-Illobre D, Li KW, Scheper W, Neurons with granulovacuolar degeneration bodies are resilient to tau-induced protein synthesis impairment. Sci Adv, 12(10):eaea8940(2026) [pubmed]

submitter keyword: resilience,granulovacuolar degeneration bodies (GVBs), tau, CK1δ

Ka Wan Li
contact affiliation	Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research,Amsterdam Neuroscience, Vrije Universiteit Amsterdam, De Boelelaan 1085,1081 HV Amsterdam, The Netherlands
contact email	k.w.li@vu.nl
lab head
Debora Pita Illobre
contact affiliation	Vrije Universiteit Amsterdam
contact email	debopita@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/2026/03/PXD061887

PRIDE project URI

• PRIDE
  1. PXD061887
     1. Label: PRIDE project
     2. Name: Casein kinase 1δ induces the formation of GVB-positive neurons that are resilient to tau-induced impairment of protein synthesis