Myeloperoxidase (MPO): Do We Need Inhibitors?
Myeloperoxidase (MPO): Do We Need Inhibitors?
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DOI：
10.1007/978-3-319-60324-7_24
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发表时间：
2017-01-01
期刊：
影响因子：
--
通讯作者：
Parthasarathy, Sampath
中科院分区：
文献类型：
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作者：
Desikan, Rajagopal;Narasimhulu, Chandrakala Aluganti;Parthasarathy, Sampath
中性粒细胞、单核细胞和选定的组织巨噬细胞是髓过氧化物酶(MPO)的主要来源。在生理氯离子浓度下，MPO血型蛋白能在另一种氧化剂过氧化氢存在下催化次氯酸的生成反应。MPO介导的氧化剂在炎症反应中起着重要的作用，但传统上认为MPO是一种非特异性的杀微生物酶，一些中间产物对免疫系统抵御入侵病原体具有重要作用。炎症在动脉粥样硬化等心血管疾病的表现和改善中起主导作用。因此，MPO作为诊断和开发有效的治疗辅助手段对抗这种氧化酶的靶点一直受到人们的关注。开发一种抑制MPO的药物的必要性正在稳步上升，通过这次综述，我们对MPO的来源、主要生理作用、目前可用的抑制剂和在计算机筛查中的应用、对MPO水平升高的有害影响及其在多种疾病进展中的意义等方面的文献现状进行了评估。我们批判性地分析了目前利用有机小分子、未开发的有机金属支架开发合适的抑制剂的努力、适体作为髓过氧化物酶抑制剂的利用以及对这一吸引人的靶点的治疗干预范围的未来前景。
Neutrophils, monocytes and selected tissue macrophages are the predominant sources of myeloperoxidase (MPO). Under physiological chloride concentration, the MPO hemo protein can catalyze the reaction of formation of hypochlorous acid in presence of another oxidant, hydrogen peroxide. MPO-mediated oxidants play a significant part in the inflammatory response, though, the MPO is traditionally viewed as an unspecific microbicidal enzyme and some intermediates are important for immune defense system against invading pathogens. Inflammation plays a lead role in the manifestation and the amelioration of atherosclerosis and other cardiovascular diseases. Hence, there is continuing interest on MPO as a target in the diagnosis and development of potent therapeutic aid against this oxidative enzyme. The necessity of developing a drug to inhibit MPO is getting steady momentum and through this review, we assess the current status of the -literature on the source of MPO, its primary physiological role, currently available inhibitors and application of in silico screening, harmful effects on the increased levels of MPO and its implication in multiple disease progression. We critically analyze current efforts toward the development of suitable inhibitors using small organic molecules, unexplored organometallic scaffolds, utilization of aptamers as myeloperoxidase inhibitor and future perspective on the scope of therapeutic intervention for this attractive target.