Targeting Atf4 for enhanced neuroprotection: Role of quercetin-loaded EVs in ischemic stroke.
10.1016/j.jpha.2025.101312
- Author:
Lanqing ZHAO
1
;
Yu CHEN
2
;
Xiaoxu DING
2
;
Hongxi LI
3
;
Jinwei LI
4
Author Information
1. Department of Sleep Medicine Center, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
2. Department of Otorhinolaryngology Head and Neck, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
3. Department of Pain Management, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
4. Department of Neurology and Stroke Center, The First Affiliated Hospital of China Medical University, China Medical University, 110001, Liaoning, China.
- Publication Type:Journal Article
- Keywords:
Atf4;
Cerebral ischemia-reperfusion injury;
Extracellular vesicles;
Neuroprotection;
Oxidative stress;
Quercetin-3-O-β-d-glucuronic acid
- From:
Journal of Pharmaceutical Analysis
2025;15(9):101312-101312
- CountryChina
- Language:English
-
Abstract:
This study investigates the neuroprotective potential of extracellular vesicles (EVs) delivering quercetin-3-O-β-d-glucuronic acid (QG-EVs) in cerebral ischemia-reperfusion injury (CIRI). Targeted brain delivery of QG-EVs was confirmed, with neuron cells identified as pivotal in modulating CIRI through single-cell RNA sequencing (scRNA-seq). Activating transcription factor 4 (Atf4) was highlighted as a critical regulatory factor, and in vitro studies revealed that silencing Atf4 diminished the neuroprotective effects of QG-EVs, increasing oxidative stress levels and neuronal apoptosis. In a CIRI mouse model, the knockdown of Atf4 attenuated the protective outcomes provided by QG-EVs, further affirming the role of Atf4 in mediating neuroprotection. Behavioral assessments and protein analysis showed that QG-EVs significantly reduced neuronal damage and pro-apoptotic markers, while improving neurological function via Atf4 upregulation. The outcomes hint at the potential of QG-EVs as a beneficial therapeutic modality to mitigate neuronal damage in CIRI by enhancing Atf4 expression, highlighting its potential for improving ischemic stroke outcomes.
