PXD037113-1

PXD037113 is an original dataset announced via ProteomeXchange.

Title	Distinct Impact of Neuronal and Astrocytic IFNAR1 Loss in Parkinson-like Dementia
Description	Interferon-alpha/beta-receptor (IFNAR) signal defects were recently identified to contribute to sporadic Parkinson’s disease (PD) with dementia (PDD). Mice lacking interferon-beta (IFNβ) develop PDD-like disease; however, the phenotypic, cellular, and molecular impacts of IFNAR1 loss in vivo have not been explored. Studying cell-specific pathology in Ifnar1–/– mice may reveal potential disease-modifying therapeutic targets for PDD. Here, we present that Ifnar1–/– mice exhibit PDD-like pathogenesis, including dopaminergic neurodegeneration in the substantia nigra, Lewy-body-like alpha-synuclein+ inclusions, gliosis-associated phosphorylated-tau and amyloid-beta proteinopathy, and progressive PDD-like behavior deficits. Hallmark neuropathology and motor and cognitive behavior deficits were specifically recapitulated in mice lacking neuronal IFNAR1. Ifnar1–/– mice also exhibited early-onset nociceptive pain and neuropsychiatric abnormalities, recapitulated in mice lacking astrocytic IFNAR1. Neuron/astrocyte-specific transcriptomic and proteomic alterations in early-manifest Ifnar1–/– mice implicate synergistic dysfunctional excitatory neurotransmission upon IFNAR1 loss, leading to glucose hypermetabolism prior to cognitive decline. Targeted restoration of dysfunctional neuronal and astrocytic IFNAR1 could therefore potentially mitigate PDD progression through concerted regulation of excitatory neurotransmission.
HostingRepository	PRIDE
AnnounceDate	2026-06-08
AnnouncementXML	Submission_2026-06-07_20:18:30.657.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Niels Henning Skotte
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-30 04:09:22	ID requested
⏵ 1	2026-06-07 20:18:31	announced

Villanueva EB, Zebec Z, Cisquella-Serra M, Lundstr, ø, m J, Andersen JV, Qvist FL, Westi EW, Marin A, Jimenez-Duran G, Riera-Ponsati L, Tresse E, Kretz O, Loreth D, Goldmann T, Blank T, Prinz M, Aldana BI, Mann M, Skotte NH, Issazadeh-Navikas S, -receptor-1 loss in neurons and astrocytes disrupt brain energy metabolism and drive Parkinsonian dementia. J Biomed Sci, 33(1):(2026) [pubmed]

10.1186/s12929-026-01257-8;

submitter keyword: IFNAR1, glutamatergic neurotransmission, snRNA-seq,Parkinson’s disease dementia, LC-MS/MS

Niels Henning Skotte
contact affiliation	Skotte Research Group Department for Drug Design and Pharmacology Molecular Neuroprotection Novo Nordisk Foundation Center for Protein Research Clinical Proteomics University of Copenhagen
contact email	niels.skotte@sund.ku.dk
lab head
Niels Henning Skotte
contact affiliation	University of Copenhagen
contact email	niels.skotte@sund.ku.dk
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/2026/06/PXD037113

PRIDE project URI

• PRIDE
  1. PXD037113
     1. Label: PRIDE project
     2. Name: Distinct Impact of Neuronal and Astrocytic IFNAR1 Loss in Parkinson-like Dementia