Lactylation of PTBP1 drives a pro-apoptotic positive feedback loop in microglia following oxygen-glucose deprivation/reoxygenation-induced injury - PubMed
3 hours ago
- #OGD/R Injury
- #Microglial Apoptosis
- #Lactylation
- Lactylation of RNA-binding splicing regulator PTBP1 is a key mechanism in microglial apoptosis following oxygen-glucose deprivation/reoxygenation (OGD/R) injury.
- Hyperlactylated PTBP1 suppresses USP18 expression, leading to FTO degradation and reduced delactylase SIRT1 activity, amplifying PTBP1 lactylation in a positive feedback loop.
- Lactylation-deficient PTBP1 mutations (K258R, K452R) attenuate apoptotic signaling, suggesting therapeutic targeting of the PTBP1-USP18-FTO-SIRT1 axis for neuroprotection.