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Thiol antioxidant thioredoxin reductase: A prospective biochemical crossroads between anticancer and antiparasitic treatments of the modern era.
International Journal of Biological Macromolecules ( IF 8.2 ) Pub Date : 2020-09-19 , DOI: 10.1016/j.ijbiomac.2020.09.096
Nikhilesh Joardar 1 , Alberto Guevara-Flores 2 , José de J Martínez-González 2 , Santi P Sinha Babu 1
Affiliation  

The thiol-based glutathione reductase (GR) and thioredoxin reductase (TrxR) are the major antioxidant enzymes present in various organisms that maintain the internal redox homeostasis. The thioredoxin system has attracted the attention of researchers from diverse investigation fields of biological sciences. Apart from redox regulation, this system is thought to be the major regulator of various biological processes including transcription, apoptosis, etc. Identification and physicobiochemical characterization of the reductase enzyme i.e. Thioredoxin reductase (TrxR) revealed the potency of it to become a promising target. Novel therapeutic interventions by selective targeting of TrxR in parasitic organisms as well as in the cancer cells have now become a usual treatment approach. However, different isoforms and their variation in the penultimate amino acid (Selenocysteine or cysteine) present in the catalytic site of the enzyme have made this enzyme to respond differently towards various drugs and synthetic and/or natural compounds. Therefore, the present article seeks to highlight the importance and the detailed molecular mechanism, functional perspective underlying the TrxR inhibition in various parasitic protozoans, helminthes as well as in cancer cells for devising suitable anti-TrxR candidates.



中文翻译:

硫醇抗氧化剂硫氧还蛋白还原酶:现代抗癌和抗寄生虫治疗之间的前瞻性生化十字路口。

基于硫醇的谷胱甘肽还原酶(GR)和硫氧还蛋白还原酶(TrxR)是存在于维持内部氧化还原稳态的各种生物体中的主要抗氧化酶。硫氧还蛋白系统引起了生物科学各个研究领域的研究人员的关注。除氧化还原调节外,该系统还被认为是包括转录,凋亡等在内的各种生物过程的主要调节剂。还原酶即硫氧还蛋白还原酶(TrxR)的鉴定和理化性质揭示了其成为有希望的靶标的潜力。通过在寄生生物以及癌细胞中选择性靶向TrxR的新型治疗手段现已成为一种常见的治疗方法。然而,存在于酶催化位点的倒数第二个氨基酸(硒代半胱氨酸或半胱氨酸)中不同的同工型及其变异,使该酶对各种药物以及合成和/或天然化合物的反应不同。因此,本文旨在强调在设计合适的抗TrxR候选物时,TrxR抑制作用在各种寄生原生动物,蠕虫以及癌细胞中的重要性和详细的分子机制,功能性观点。

更新日期:2020-10-02
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