Biologics : targets & therapy · 2025
ATF3 Knockdown Exacerbates Astrocyte Activation by Inhibiting Phosphorylation of Drp1 in Ischemic Stroke.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
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Huang Rong, Huang Xiaoyan, Yang Hongmei, Wu Haixuan, Liu Fan, Saw Phei Er, Cao Minghui
Аннотация
INTRODUCTION: ATF3, a stress-induced transcription factor, has been implicated in the injury processes of various cell types, including neurons. It is recognized as a common marker for neuronal damage following neurotrauma. However, its role in other types of glial cells, particularly astrocytes, in response to ischemic injury remains unclear. Mitochondrial dysfunction is a key factor in the pathogenesis of ischemic stroke, and impaired mitochondrial function in astrocytes is associated with astrocyte activation. This study aimed to explore the relationship between mitochondrial damage and ischemic stroke and to investigate how ATF3 regulates mitochondrial dysfunction and astrocyte activation in the context of ischemic injury.
METHODS: In a transient middle cerebral artery occlusion (tMCAO) mouse model, we knocked down ATF3 and assessed infarct size, motor deficits, astrocyte activation, and mitochondrial damage. In vitro, we used oxygen-glucose deprivation and reoxygenation (OGD-R) to simulate ischemia and evaluated the impact of ATF3 knockdown on astrocyte activation and mitochondrial function.
RESULTS: ATF3 knockdown exacerbated infarct size, motor deficits, and astrocyte activation in vivo, with increased mitochondrial damage. In vitro, ATF3 depletion worsened mitochondrial dysfunction and astrocyte activation. ATF3 interacted with Drp1 via Akt2, inhibiting mitochondrial fission and protecting astrocytes.
CONCLUSION: ATF3 regulates mitochondrial fission and protects astrocytes in ischemic stroke, highlighting its potential as a therapeutic target for stroke recovery.
METHODS: In a transient middle cerebral artery occlusion (tMCAO) mouse model, we knocked down ATF3 and assessed infarct size, motor deficits, astrocyte activation, and mitochondrial damage. In vitro, we used oxygen-glucose deprivation and reoxygenation (OGD-R) to simulate ischemia and evaluated the impact of ATF3 knockdown on astrocyte activation and mitochondrial function.
RESULTS: ATF3 knockdown exacerbated infarct size, motor deficits, and astrocyte activation in vivo, with increased mitochondrial damage. In vitro, ATF3 depletion worsened mitochondrial dysfunction and astrocyte activation. ATF3 interacted with Drp1 via Akt2, inhibiting mitochondrial fission and protecting astrocytes.
CONCLUSION: ATF3 regulates mitochondrial fission and protects astrocytes in ischemic stroke, highlighting its potential as a therapeutic target for stroke recovery.