ACSL4 exacerbates ischemic stroke by promoting ferroptosis-induced brain injury and neuroinflammation.

Yu Cui, Yan Zhang, Xiaolong Zhao, Liming Shao, Guoping Liu, Chengjian Sun, Rui Xu, Zhaolong Zhang

Brain, behavior, and immunity 2021 Mar

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Acyl-CoA synthetase long-chain family member 4 (ACSL4) is an important isozyme for polyunsaturated fatty acids (PUFAs) metabolism that dictates ferroptosis sensitivity. The role of ACSL4 in the progression of ischemic stroke is unclear. Here, we found that ACSL4 expression was suppressed in the early phase of ischemic stroke and this suppression was induced by HIF-1α. Knockdown of ACSL4 protected mice against brain ischemia, whereas, forced overexpression of ACSL4 exacerbated ischemic brain injury. ACSL4 promoted neuronal death via enhancing lipid peroxidation, a marker of ferroptosis. Moreover, knockdown of ACSL4 inhibited proinflammatory cytokine production in microglia. These data identify ACSL4 as a novel regulator of neuronal death and neuroinflammation, and interventions of ACSL4 expression may provide a potential therapeutic target in ischemic stroke. Copyright © 2021 Elsevier Inc. All rights reserved.

Citation

Yu Cui, Yan Zhang, Xiaolong Zhao, Liming Shao, Guoping Liu, Chengjian Sun, Rui Xu, Zhaolong Zhang. ACSL4 exacerbates ischemic stroke by promoting ferroptosis-induced brain injury and neuroinflammation. Brain, behavior, and immunity. 2021 Mar;93:312-321