PXD071487-1

PXD071487 is an original dataset announced via ProteomeXchange.

Title	SIRT1 mediates brain metabolic and developmental consequences of methionine synthase deficiency in inborn errors of cobalamin metabolism
Description	Inborn errors of vitamin B12 metabolism (IECM) resulting from impaired methionine synthase (MS, encoded by MTR) activity cause severe cognitive and neurological deficits that are often unresponsive to conventional B12 supplementation. Using a brain-specific Mtr knockout mouse model, we identified the NAD⁺-dependent deacetylase SIRT1 as a central regulator of the pathological phenotype, and evaluated the therapeutic efficacy of its pharmacological activator, SRT2104. MS deficiency led to profound metabolic, mitochondrial, and epigenomic alterations in the hippocampus, including promoter hypermethylation of the pyruvate dehydrogenase complex, impaired TCA cycle activity, and reduced SIRT1 expression. At the functional level, we observed a disruption of Wnt signaling, associated with decreased neurogenesis, increased astrocytosis, and cognitive impairment. Treatment with SRT2104 effectively restored mitochondrial and energy metabolism, normalized Wnt signaling and neurogenesis markers, and rescued learning and memory performance. These findings identify SIRT1 as a potential therapeutic target in B12-related neurodevelopmental disorders and support the clinical repurposing of SRT2104 to alleviate persistent neurological symptoms.
HostingRepository	PRIDE
AnnounceDate	2026-01-06
AnnouncementXML	Submission_2026-01-06_08:23:06.954.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Guillaume CHEVREUX
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-02 15:24:01	ID requested
⏵ 1	2026-01-06 08:23:07	announced

Dataset with its publication pending

submitter keyword: vitamin B12 deficiency,methionine synthase, One-carbon metabolism, Wnt signaling, Inborn errors of cobalamin metabolism, SIRT1

Neurogenesis, Energy metabolism

GUEANT-RODRIGUEZ, Rosa-Maria
contact affiliation	Inserm UMRS 1256 N-GERE (Nutrition-Genetics-Environmental Risks)
contact email	rosa-maria.gueant-rodriguez@univ-lorraine.fr
lab head
Guillaume CHEVREUX
contact affiliation	Institut Jacques Monod, CNRS UMR7592
contact email	guillaume.chevreux@ijm.fr
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/2026/01/PXD071487

PRIDE project URI

• PRIDE
  1. PXD071487
     1. Label: PRIDE project
     2. Name: SIRT1 mediates brain metabolic and developmental consequences of methionine synthase deficiency in inborn errors of cobalamin metabolism