| First Author | Lee JH | Year | 2026 |
| Journal | Cell Metab | PubMed ID | 42049021 |
| Mgi Jnum | J:386826 | Mgi Id | MGI:8349983 |
| Doi | 10.1016/j.cmet.2026.04.001 | Citation | Lee JH, et al. (2026) Oxidative stress-induced astrocytic collagen biosynthesis drives glial barrier formation and neuronal death in ischemic stroke. Cell Metab |
| abstractText | Astrocytes regulate brain metabolism and homeostasis, but how oxidative stress reshapes astrocytic metabolism to drive neuronal damage remains unclear. Here, we demonstrate that oxidative stress turns on astrocytic type I collagen (COL1) production via a redox-glycosylation coupling mechanism. Hydrogen peroxide (H(2)O(2)) suppresses miR-29 and enhances fucosyltransferase 8 (FUT8)-mediated core fucosylation, integrating post-transcriptional and glycosylation-dependent regulation of COL1. Astrocyte-derived COL1 activates integrin signaling and promotes neuronal death. In a photothrombotic stroke model, an H(2)O(2) surge induces astrogliosis, glycosylation remodeling, and COL1 expression, leading to glial barrier formation, neuronal loss, and neurological deficits. These pathological cascades are mitigated by astrocyte-specific silencing of COL1 or FUT8 or by KDS12025, a peroxidase enhancer that reduces H(2)O(2) burden. Notably, KDS12025 exerts potent neuroprotection in a non-human primate stroke model. Together, our findings identify an unprecedented astrocytic metabolic pathway linking oxidative stress to glycosylation-driven COL1 production, highlighting the H(2)O(2) surge, astrocytic COL1, and FUT8 as promising therapeutic targets for recovery after stroke. |
