白三烯受体拮抗剂孟鲁司特作为多发性硬化症的潜在辅助治疗药物--综述

IF 4.4 2区 医学 Q1 PHARMACOLOGY & PHARMACY Frontiers in Pharmacology Pub Date : 2024-09-13 DOI:10.3389/fphar.2024.1450493
Frank Pietrantonio, Alex Serreqi, Horst Zerbe, Per Svenningsson, Ludwig Aigner
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摘要

多发性硬化症(MS)是中枢神经系统(CNS)的一种多因素自身免疫性疾病。它的特点是免疫系统高度激活,随之而来的是炎症、脱髓鞘和神经变性,并导致运动、感觉、认知和自主神经功能障碍等后果。虽然一系列免疫调节药物在缓解病理和症状方面显示出一定的疗效,但目前可用的治疗方法都无法使受损的中枢神经系统再生以恢复功能。有新证据表明,白三烯和白三烯受体参与了多发性硬化症病理的各个方面,包括神经炎症和脱髓鞘。此外,白三烯受体拮抗剂,如哮喘药物孟鲁司特,可减轻炎症反应,促进再生/脱髓鞘。事实上,孟鲁司特已成功地在多发性硬化症动物模型中进行了测试,最近的一项回顾性病例对照研究表明,孟鲁司特治疗可减少多发性硬化症患者的复发。因此,我们建议将孟鲁司特作为标准免疫调节药物的辅助治疗药物,以减少病理变化并促进结构和功能的恢复。在此,我们回顾了有关多发性硬化症及其病理的现有知识,以及白三烯受体拮抗剂作为多发性硬化症治疗药物的潜力。
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The leukotriene receptor antagonist montelukast as a potential therapeutic adjuvant in multiple sclerosis – a review
Multiple Sclerosis (MS) is a multifactorial autoimmune disease of the central nervous system (CNS). It is characterized by a heightened activation of the immune system with ensuing inflammation, demyelination and neurodegeneration with consequences such as motor, sensory, cognitive, as well as autonomic dysfunctions. While a range of immune-modulatory drugs have shown certain efficacy in alleviating pathology and symptoms, none of the currently available therapeutics regenerates the damaged CNS to restore function. There is emerging evidence for leukotrienes and leukotriene receptors being involved in the various aspects of the MS pathology including neuroinflammation and de/remyelination. Moreover, leukotriene receptor antagonists such as the asthma drug montelukast diminish inflammation and promote regeneration/remyelination. Indeed, montelukast has successfully been tested in animal models of MS and a recent retrospective case-control study suggests that montelukast treatment reduces relapses in patients with MS. Therefore, we propose montelukast as a therapeutic adjuvant to the standard immune-modulatory drugs with the potential to reduce pathology and promote structural and functional restoration. Here, we review the current knowledge on MS, its pathology, and on the potential of leukotriene receptor antagonists as therapeutics for MS.
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来源期刊
Frontiers in Pharmacology
Frontiers in Pharmacology PHARMACOLOGY & PHARMACY-
CiteScore
7.80
自引率
8.90%
发文量
5163
审稿时长
14 weeks
期刊介绍: Frontiers in Pharmacology is a leading journal in its field, publishing rigorously peer-reviewed research across disciplines, including basic and clinical pharmacology, medicinal chemistry, pharmacy and toxicology. Field Chief Editor Heike Wulff at UC Davis is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
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