PXD056011-1

PXD056011 is an original dataset announced via ProteomeXchange.

Title	Magnetic resonance imaging and transcriptome-proteome integration analysis demonstrate improved disease-outcome in the cuprizone mouse model following AAV-mediated delivery of A Proliferation Inducing Ligand
Description	A Proliferation Inducing Ligand (APRIL) is a member of the tumour necrosis factor (TNF) superfamily and has recently been shown to modulate pro-inflammatory astrocyte responses, as well as to ameliorate disease outcome in the experimental autoimmune encephalomyelitis mouse model for multiple sclerosis (MS). In this new study, an unbiased proteomic analysis first confirmed that adeno-associated virus (AAV)-mediated delivery of APRIL was able to rescue immune-stimulated murine iPSC-derived neurospheroids from detrimental cell death and neurodegenerative processes. Next, we investigated whether AAV-mediated secretion of APRIL by cortical neurons could influence cuprizone-induced neuro-inflammation and/or demyelination in the splenium of the corpus callosum. Applying both T2 and diffusion-weighted magnetic resonance imaging (MRI), with subsequent histological confirmation, our results indicated that cortical secretion of APRIL is able to reduce neuro-inflammatory and demyelinating events in the splenium. To further document the beneficial effect of APRIL, a transcriptome-proteome integration study for the splenium revealed the activation of cellular pathways associated with alternative immune cell polarisation, cell survival and neuroregeneration. Lastly, even though our MRI and transcriptome-proteome integration study for the cortical AAV injection site noted a local activation of cellular pathways associated with inflammation, these events were not associated with major abnormalities in histological appearance. Concluding, our findings highlight that APRIL has strong anti-inflammatory and neuroprotective effects in the CNS which may have the potential to improve MS-like disease outcome.
HostingRepository	PRIDE
AnnounceDate	2025-11-10
AnnouncementXML	Submission_2025-11-09_16:35:08.054.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Federica Di Marco
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-19 03:42:40	ID requested
⏵ 1	2025-11-09 16:35:09	announced

10.1186/s12974-025-03569-2;

Ricciardi L, Di Marco F, Decrop M, Di Stefano J, Kakunuri T, van Rijswijk J, Vidas-Guscic N, El Ouaamari Y, Bufi AA, Van Spilbeeck I, Van Audekerke J, Faghel C, Bartholomeus E, Lion E, Cools N, Van Laere S, Cicalini I, De Laurenzi V, FitzGerald U, Pieragostino D, Huard B, Del Boccio P, Ponsaerts P, Verhoye M, AAV-mediated delivery of a proliferation inducing ligand (APRIL) to cortical neurons limits inflammation and demyelination in the corpus callosum of the cuprizone mouse model. J Neuroinflammation, 22(1):240(2025) [pubmed]

submitter keyword: Cuprizone, Adeno-associated Virus, Neuroprotection, Neuroinflammation, Magnetic Resonance Imaging, Transcriptomics, Proteomics,APRIL

Peter Ponsaerts
contact affiliation	Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, 2610 Wilrijk, Belgium
contact email	peter.ponsaerts@uantwerpen.be
lab head
Federica Di Marco
contact affiliation	University of "G. d' Annunzio" Chieti - Pescara
contact email	federica.dimarco@unich.it
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056011
     1. Label: PRIDE project
     2. Name: Magnetic resonance imaging and transcriptome-proteome integration analysis demonstrate improved disease-outcome in the cuprizone mouse model following AAV-mediated delivery of A Proliferation Inducing Ligand