PXD069980-1

PXD069980 is an original dataset announced via ProteomeXchange.

Title	Molecular Insights into Central Core Disease: Proteomic Signatures and Potential Therapeutic Biomarkers in RYR1 I4895T Mice
Description	Central Core Disease (CCD) is a congenital myopathy, predominantly caused by mutations in the gene encoding for ryanodine receptor type-1(RYR1), the intracellular Ca2+ release channel embedded in skeletal muscle sarcoplasmic reticulum membrane. One of the most common RYR1 mutations associated to CCD is represented by the I4898T. Unfortunately, there are no approved therapies for CCD and for other myopathies caused by mutations in gene. This study aims to perform a top-down differential proteomic analysis on soleus tissue samples from wild-type mice (WT) and heterozygous knock mice carrying the- I4895T (IT) mutation in RyR1, to investigate pathogenic mechanisms and molecular pathways involved in this myopathy and to shed light on new potential biomarkers useful for future therapies. Proteomic analysis revealed 50 dysregulated protein species and multivariate analysis shows that IT mice exhibit a distinct proteomic signature compared to WT mice, characterized by alterations in proteins associated with contractile and structural dysfunction, metabolism, and stress response. In particular, a significant increase in myosin fragments was observed in IT mice, likely due to muscle breakdown. In contrast, myotilin was downregulated, suggesting a weakening of muscle cytoskeletal structure. There was a notable downregulation of proteins involved in glycolysis and TCA cycle; conversely, there was an increase in proteins related to anaerobic glycolysis, suggesting a shift from aerobic to anaerobic glycolysis. Furthermore, proteins involved in fatty acid beta-oxidation and oxidative phosphorylation were also found to be up regulated in IT mice, indicating an attempt by the muscle to maximize energy production. Finally, we found a significant decrease in PGC1α, which could serve as potential target-therapy biomarker in CCD.
HostingRepository	PRIDE
AnnounceDate	2025-12-22
AnnouncementXML	Submission_2025-12-21_16:07:51.581.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Lorenza Vantaggiato
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	iodoacetamide derivatized residue
Instrument	ultraflex

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-28 06:47:16	ID requested
⏵ 1	2025-12-21 16:07:52	announced

10.3390/ijms262311451;

Vantaggiato L, Shaba E, Fiore F, Rossi D, Sorrentino V, Bini L, Landi C, Molecular Insights into Central Core Disease: Proteomic Signatures and Potential Therapeutic Biomarkers in RYR1 I4895T Mice. Int J Mol Sci, 26(23):(2025) [pubmed]

submitter keyword: oxidative phosphorylation, myosin fragments,Central Core Disease, glycolysis, PGC1α

Luca Bini
contact affiliation	Functional Proteomics Lab., Dept Life Sciences, University of Siena.
contact email	luca.bini@unisi.it
lab head
Lorenza Vantaggiato
contact affiliation	University of Siena
contact email	lorenz.vantaggiato2@unisi.it
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD069980
     1. Label: PRIDE project
     2. Name: Molecular Insights into Central Core Disease: Proteomic Signatures and Potential Therapeutic Biomarkers in RYR1 I4895T Mice