Phosphatidic Acid‐TRIM59‐Olig2 Signaling Couples Metabolic Dysfunction to Myelination Failure in PWMI
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Le résumé fourni par la source
Cerebral palsy (CP), mainly resulting from preterm white matter injury (PWMI), remains a leading neurodevelopmental disorder. While oligodendrocyte precursor cell (OPC) differentiation failure is central to PWMI pathology, the metabolic mechanisms remain unclear. Here, untargeted lipidomic and metabolomic profiling of serum samples from retrospective and prospective cohorts of preterm infants identified a CP-associated metabolic signature, highlighting phosphatidic acid (PA) as a top candidate that was consistently elevated and showed strong discriminative potential. Increased PA levels were validated in both serum and brains of PWMI mice and in OPCs subjected to oxygen-glucose deprivation/reoxygenation (OGD/R), where PA impaired OPC differentiation and myelination. Mechanistically, PA interacted with and stabilized the E3 ubiquitin ligase TRIM59, increasing its protein abundance and half-life without affecting mRNA levels. Elevated TRIM59 promoted proteasomal degradation of the oligodendrocyte lineage transcription factor Olig2, a key regulator of OPC maturation. Inhibition of PA synthesis restored Olig2 expression, improved myelination, and rescued differentiation deficits in PWMI mice. Collectively, this study identifies PA as a potential metabolic risk factor associated with preterm CP and uncovers a PA-TRIM59-Olig2 signaling axis linking lipid metabolism to OPC differentiation failure and PWMI.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Phosphatidic Acid‐TRIM59‐Olig2 Signaling Couples Metabolic Dysfunction to Myelination Failure in PWMI
- Date Crossref
- 18/02/2026
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Xuzhou Medical College pays non établi dans la noticeUniversité ou école supérieure
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Yuhuangding Hospital Yantai Municipal Key Medical and Health Laboratory of Yantai Yuhuangding Hospital (Interdisciplinary Brain Science and Geriatric Health Laboratory) pays non établi dans la noticeÉtablissement de santé
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Department of Cell Biology and Neurobiology Xuzhou Key Laboratory of Neurobiology Xuzhou Medical University Xuzhou Jiangsu Province China pays non établi dans la noticeUniversité ou école supérieure
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Department of Human Anatomy Xuzhou Medical University Xuzhou Jiangsu Province China pays non établi dans la noticeUniversité ou école supérieure
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Department of Neurology Affiliated Hospital of Xuzhou Medical University Xuzhou Jiangsu Province China pays non établi dans la noticeUniversité ou école supérieure
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Department of Urology Affiliated Hospital of Xuzhou Medical University Xuzhou Jiangsu Province China pays non établi dans la noticeUniversité ou école supérieure
Xuzhou Medical College, Yantai Municipal Key Medical and Health Laboratory of Yantai Yuhuangding Hospital (Interdisciplinary Brain Science and Geriatric Health Laboratory) — Yuhuangding Hospital et Department of Cell Biology and Neurobiology Xuzhou Key Laboratory of Neurobiology Xuzhou Medical University Xuzhou Jiangsu Province China, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.