Wang Xuening, Shao Qiuji, Gao Yuan
Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China; Institute of Clinical Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China.
Department of Cerebrovascular Disease, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China.
Brain Res Bull. 2025 Feb;221:111194. doi: 10.1016/j.brainresbull.2025.111194. Epub 2025 Jan 7.
The arachidonic acid metabolic pathway is a classic inflammatory pathway. 12/15-lipoxygenase (LOX), a member of the lipoxygenase family that metabolizes arachidonic acid, has been implicated in the pathogenesis of numerous central nervous system (CNS) diseases. Ischemic stroke is a devastating disease in which the occlusion of cerebral arteries leads to a series of pathophysiological changes in brain tissue, triggering an inflammatory cascade within the brain that results in neuroinflammation. Prior research has shown that 12/15-LOX levels in the brain are elevated following stroke. In this review, we elaborate on the key pathological mechanisms that unfold following ischemic stroke, including neuroinflammation, oxidative stress, neuronal apoptosis, and blood-brain barrier disruption, and present evidence demonstrating that 12/15-LOX inhibition could be used to treat ischemic stroke through various avenues. Furthermore, we list currently available inhibitors of 12/15-LOX and the preclinical or clinical applications, offering novel insights for the early diagnosis, prognosis evaluation, and targeted therapy in neurological diseases.
花生四烯酸代谢途径是一条经典的炎症途径。12/15-脂氧合酶(LOX)是脂氧合酶家族的成员之一,可代谢花生四烯酸,它与多种中枢神经系统(CNS)疾病的发病机制有关。缺血性中风是一种破坏性疾病,脑动脉闭塞会导致脑组织发生一系列病理生理变化,引发脑内炎症级联反应,进而导致神经炎症。先前的研究表明,中风后大脑中的12/15-LOX水平会升高。在这篇综述中,我们阐述了缺血性中风后出现的关键病理机制,包括神经炎症、氧化应激、神经元凋亡和血脑屏障破坏,并提供证据证明抑制12/15-LOX可通过多种途径用于治疗缺血性中风。此外,我们列出了目前可用的12/15-LOX抑制剂及其临床前或临床应用,为神经疾病的早期诊断、预后评估和靶向治疗提供了新的见解。