Pharmaceutical Medicine, Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India.
School of Pharmaceutical Sciences, Apeejay Stya University, Sohna-Palwal Road, Sohna, Gurgaon 122013, Haryana, India.
Eur J Pharmacol. 2019 Jan 5;842:208-220. doi: 10.1016/j.ejphar.2018.10.040. Epub 2018 Oct 30.
Cysteinyl leukotrienes (cysLTs) are member of eicosanoid inflammatory lipid mediators family produced by oxidation of arachidonic acid by action of the enzyme 5-lipoxygenase (5-LOX). 5-LOX is activated by enzyme 5-Lipoxygenase-activating protein (FLAP), which further lead to production of cysLTs i.e. leukotriene C4 (LTC4), leukotriene D4 (LTD4) and leukotriene E4 (LTE4). CysLTs then produce their potent inflammatory actions by activating CysLT1 and CysLT2 receptors. Inhibitors of cysLTs are indicated in asthma, allergic rhinitis and other inflammatory disorders. Earlier studies have associated cysLTs and their receptors in several neurodegenerative disorders diseases like, multiple sclerosis, Parkinson's disease, Huntington's disease, epilepsy and Alzheimer's disease (AD). These inflammatory lipid mediators have previously shown effects on various aggravating factors of AD. However, not much data has been elucidated to test their role against AD clinically. Herein, through this review, we have provided the current and emerging information on the role of cysLTs and their receptors in various neurological complications responsible for the development of AD. In addition, literature evidences for the effect of cysLT inhibitors on distinct aspects of abnormalities in AD has also been reviewed. Promising advancement in understanding on the role of cysLTs on the various neuromodulatory processes and mechanisms may contribute to the development of newer and safer therapy for the treatment of AD in future.
半胱氨酰白三烯(cysLTs)是花生四烯酸经 5-脂氧合酶(5-LOX)作用氧化产生的类二十烷素炎症脂质介质家族的成员。5-LOX 被 5-脂氧合酶激活蛋白(FLAP)激活,这进一步导致 cysLTs 的产生,即白三烯 C4(LTC4)、白三烯 D4(LTD4)和白三烯 E4(LTE4)。cysLTs 然后通过激活 CysLT1 和 CysLT2 受体产生其有效的炎症作用。cysLTs 抑制剂用于哮喘、过敏性鼻炎和其他炎症性疾病。早期的研究已经将 cysLTs 及其受体与几种神经退行性疾病联系起来,如多发性硬化症、帕金森病、亨廷顿病、癫痫和阿尔茨海默病(AD)。这些炎症性脂质介质先前已经显示出对 AD 的各种加重因素的影响。然而,没有太多的数据已经阐明测试它们在临床上对 AD 的作用。在此,通过这项综述,我们提供了关于 cysLTs 及其受体在 AD 发展过程中导致的各种神经并发症中的作用的最新和新兴信息。此外,还综述了 cysLT 抑制剂对 AD 不同方面异常的作用的文献证据。对半胱氨酰白三烯在各种神经调节过程和机制中的作用的理解的有希望的进展可能有助于为未来 AD 的治疗开发更新、更安全的治疗方法。