摘要
氧化应激,人类基因组不稳定性的关键因素之一,参与许多疾病的DNA损伤与修复(DDR),如神经异常及癌症相关疾病等。具有DDR通路缺陷的患者显示其肿瘤易感性水平很高,同时显示为脑积水,痴呆、甚至糖尿病,这些均为线粒体相关疾病的共同特征。线粒体在细胞能量代谢和活性氧/氮物族(RO/NS)的形成过程中起着重要作用,线粒体功能障碍(MDF)在上述疾病中发挥了举足轻重的作用。毋庸置疑,RO/NS被认为是大量化合物的一个主要靶点,旨在消除这些有害物质,或者与此相反,提高其存在活性,以扩大细胞死亡途径。然而,只有少数化学物质已得到医学上的肯定,主要因其在健康状态下的有争议的治疗价值观。因此,最近精力都集中在寻找药物,改善线粒体功能或化学预防MDF效果而不是被用作RO/NS清除剂。本文综述了化学物质开发和应用方面的最新进展,并展望了其未来发展方向。
关键词: 凋亡,化学预防,线粒体,线粒体自噬,氧化应激,RNS,ROS
Current Medicinal Chemistry
Title:Mitochondria-Mediated Oxidative Stress: Old Target for New Drugs
Volume: 22 Issue: 26
Author(s): Alex Lyakhovich and Dmitri Graifer
Affiliation:
关键词: 凋亡,化学预防,线粒体,线粒体自噬,氧化应激,RNS,ROS
摘要: Oxidative stress, one of the crucial factors of genomic instability, is involved in many illnesses - from DNA damage and repair (DDR) related diseases to neurological abnormalities and cancer. Patients with defective DDR pathways display high level of cancer predisposition and at the same time - reveal hydrocephalia, dementias and even diabetes mellitus - all representing common hallmarks of mitochondria-related disorders. Since mitochondria are responsible both for the cell energetic metabolism and for reactive oxygen/nitrogen species (RO/NS) formation, mitochondrial dysfunction (MDF) play a pivotal role in the above disorders. Not surprisingly, RO/NS are considered to be a primary target for a large spectrum of compounds aiming to eliminate these adverse species or, in contrary, enhance their presence in order to amplify cellular death pathways. Yet, only few chemicals have received medical appreciation mainly because of their questionable therapeutic values in healthy states. As a result, recent efforts have been focused on finding the drugs that improve mitochondrial functions or chemoprevent MDF rather than being applied as RO/NS scavengers. This review addresses the most recent progress in the development and application of such chemicals and outlines some future perspectives.
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Cite this article as:
Lyakhovich Alex and Graifer Dmitri, Mitochondria-Mediated Oxidative Stress: Old Target for New Drugs, Current Medicinal Chemistry 2015; 22 (26) . https://dx.doi.org/10.2174/0929867322666150729114036
DOI https://dx.doi.org/10.2174/0929867322666150729114036 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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