Comprehensive Evaluation of YJ-2 as a PAD4 Inhibitor in Alleviating Ischemic Brain Injury: From NETs-Induced Neurotoxicity to In Vivo Neuroprotection.
Y, J., A, T., K, W., MM, T., R, C., L, C., H, S., D, Z., & Y, W. (2026). Comprehensive Evaluation of YJ-2 as a PAD4 Inhibitor in Alleviating Ischemic Brain Injury: From NETs-Induced Neurotoxicity to In Vivo Neuroprotection.. CNS neuroscience & therapeutics. https://doi.org/10.1002/cns.71032
Y J, A T, K W, MM T, R C, L C, et al. Comprehensive Evaluation of YJ-2 as a PAD4 Inhibitor in Alleviating Ischemic Brain Injury: From NETs-Induced Neurotoxicity to In Vivo Neuroprotection.. CNS neuroscience & therapeutics. 2026; doi: 10.1002/cns.71032
Y J, A T, K W, et al. Comprehensive Evaluation of YJ-2 as a PAD4 Inhibitor in Alleviating Ischemic Brain Injury: From NETs-Induced Neurotoxicity to In Vivo Neuroprotection.[J]. CNS neuroscience & therapeutics. 2026. DOI: 10.1002/cns.71032.
@article{y2026,
author = {Jia Y and Taledaohan A and Wang K and Tuohan MM and Chen R and Chan L and Shen H and Zhu D and Wang Y},
title = {Comprehensive Evaluation of YJ-2 as a PAD4 Inhibitor in Alleviating Ischemic Brain Injury: From NETs-Induced Neurotoxicity to In Vivo Neuroprotection.},
journal = {CNS neuroscience & therapeutics},
year = {2026},
doi = {10.1002/cns.71032},
note = {PMID: 42455114},
}
TY - JOUR AU - Jia Y AU - Taledaohan A AU - Wang K AU - Tuohan MM AU - Chen R AU - Chan L AU - Shen H AU - Zhu D AU - Wang Y TI - Comprehensive Evaluation of YJ-2 as a PAD4 Inhibitor in Alleviating Ischemic Brain Injury: From NETs-Induced Neurotoxicity to In Vivo Neuroprotection. T2 - CNS neuroscience & therapeutics PY - 2026 DO - 10.1002/cns.71032 AN - PMID:42455114 ER -
AIMS: To evaluate the neuroprotective potential of YJ-2, a novel peptidylarginine deiminase 4 (PAD4) inhibitor, against ischemia/reperfusion brain injury by targeting neutrophil extracellular trap (NET) formation. METHODS: In vitro, a NETs-induced injury model was established using SH-SY5Y and bEnd.3 cells. YJ-2's effects on viability, apoptosis, oxidative stress, and barrier permeability were assessed via CCK-8, flow cytometry, and FITC-dextran assays. In vivo, a rat middle cerebral artery occlusion/reperfusion (MCAO/R) model received YJ-2 (10 μmol/kg) intravenously. Outcomes included infarct volume (TTC staining), neurological score, neuronal apoptosis (TUNEL), and oxidative markers (ELISA). PAD4 activity and histone H3 citrullination (H3cit) were examined by western blot and immunofluorescence. RESULTS: YJ-2 reduced NET-mediated neuronal death and oxidative stress in vitro, and improved endothelial barrier integrity. In MCAO/R rats, YJ-2 significantly lowered infarct volume (44.2% → 30.6%), improved neurological function, and suppressed apoptosis. It also decreased PAD4 and H3cit expression in ischemic brain tissue, confirming target engagement. CONCLUSION: YJ-2, by preserving blood-brain barrier (BBB) integrity and reducing neuronal apoptosis, highlights its therapeutic potential for ischemic stroke.