Zhuo Bifang, Qin Chenyang, Deng Shizhe, Jiang Hailun, Si Shangkun, Tao Feng, Cai Fei, Meng Zhihong
First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China.
Mol Cell Biochem. 2025 Apr;480(4):2223-2246. doi: 10.1007/s11010-024-05150-6. Epub 2024 Nov 4.
Stroke, as a neurological disorder with a poor overall prognosis, has long plagued the patients. Current stroke therapy lacks effective treatments. Ferroptosis has emerged as a prominent subject of discourse across various maladies in recent years. As an emerging therapeutic target, notwithstanding its initial identification in tumor cells associated with brain diseases, it has lately been recognized as a pivotal factor in the pathological progression of stroke. Acyl-CoA synthetase long-chain family member 4 (ACSL4) is a potential target and biomarker of catalytic unsaturated fatty acids mediating ferroptosis in stroke. Specifically, the upregulation of ACSL4 leads to heightened accumulation of lipid peroxidation products and reactive oxygen species (ROS), thereby exacerbating the progression of ferroptosis in neuronal cells. ACSL4 is present in various tissues and involved in multiple pathways of ferroptosis. At present, the pharmacological mechanisms of targeting ACSL4 to inhibit ferroptosis have been found in many drugs, but the molecular mechanisms of targeting ACSL4 are still in the exploratory stage. This paper introduces the physiopathological mechanism of ACSL4 and the current status of the research involved in ferroptosis crosstalk and epigenetics, and summarizes the application status of ACSL4 in modern pharmacology research, and discusses the potential application value of ACSL4 in the field of stroke.
中风作为一种总体预后较差的神经系统疾病，长期以来一直困扰着患者。目前的中风治疗缺乏有效的治疗方法。近年来，铁死亡已成为各种疾病中一个突出的话题。作为一个新兴的治疗靶点，尽管它最初是在与脑部疾病相关的肿瘤细胞中被发现的，但最近它被认为是中风病理进展中的一个关键因素。酰基辅酶A合成酶长链家族成员4（ACSL4）是介导中风中铁死亡的催化不饱和脂肪酸的潜在靶点和生物标志物。具体而言，ACSL4的上调导致脂质过氧化产物和活性氧（ROS）的积累增加，从而加剧神经元细胞中铁死亡的进展。ACSL4存在于各种组织中，并参与铁死亡的多种途径。目前，在许多药物中已经发现了靶向ACSL4抑制铁死亡的药理机制，但靶向ACSL4的分子机制仍处于探索阶段。本文介绍了ACSL4的生理病理机制以及铁死亡相互作用和表观遗传学相关研究的现状，总结了ACSL4在现代药理学研究中的应用情况，并探讨了ACSL4在中风领域的潜在应用价值。
