摘要
背景:线粒体在ATP生成过程中起着核心作用。事实上,在哺乳动物组织中,高达90%的ATP是由线粒体通过氧化磷酸化过程产生的;此外,线粒体参与多种信号转导途径。许多文献已经证实线粒体在细胞凋亡、心和神经保护以及各种神经退行性疾病中起着关键性的作用,例如从帕金森到阿尔茨海默病。线粒体也是多种药物的靶标,其中一些是专门设计用来影响线粒体功能的,而另一些药物在其他细胞位置具有主要靶点,但可能与线粒体相互作用,因为在该细胞器上存在许多靶点。在这方面,线粒体钾(MITOK)通道在线粒体功能中起关键作用,并因此在整个细胞的代谢中起关键作用。 目的:从结构的角度描述MITOK通道,并探讨其病理生理作用,着眼于可能的特异性调节剂,使其成为可能作为治疗MITOK参与的各种病理学的有用工具。 结果:MITOK通道在包括心血管疾病,特别是心肌梗死和神经退行性疾病在内的多种病症中起着决定性的作用,并且正在成为有开发前景的肿瘤靶点。 结论:MITOK通道代表了新的靶点,MITOK通道调节剂是一种令人兴奋的药物干预工具。
关键词: 线粒体钾通道,心血管疾病,神经系统疾病,肿瘤疾病,磷酸化,活性氧。
Current Medicinal Chemistry
Title:Pathophysiological Role of Mitochondrial Potassium Channels and their Modulation by Drugs
Volume: 25 Issue: 23
关键词: 线粒体钾通道,心血管疾病,神经系统疾病,肿瘤疾病,磷酸化,活性氧。
摘要: Background: Mitochondria play a central role in ATP-generating processes. Indeed, in mammalian tissues, up to 90% of ATP is generated by mitochondria through the process of oxidative phosphorylation; furthermore, mitochondria are involved in multiple signal transduction pathways. A rapidly expanding body of literature has confirmed that mitochondria play a pivotal role in apoptosis, cardio- and neuro-protection, and various neurodegenerative disorders, ranging from Parkinson’s to Alzheimer’s disease. Mitochondria are also the targets of multiple drugs, some of these are specifically designed to affect mitochondrial function, while others have primary targets in other cellular locations but may interact with mitochondria because of the presence of numerous targets on this organelle. In this regard, mitochondrial potassium (mitoK) channels play a critical role in mitochondrial function and, consequently, in the metabolism of the whole cell.
Objective: To describe mitoK channels from a structural point of view and investigate their pathophysiological roles, focusing on possible specific modulators that might be useful as pharmacological tools in the treatment of various pathologies characterized by mitoK involvement.
Results: mitoK channels play a decisive role in several pathologies, including cardiovascular diseases, particularly in myocardial infarction and neurodegenerative diseases, and they are emerging as promising oncological targets.
Conclusions: mitoK channels represent novel targets, and mitoK channel modulators represent an exciting tool for pharmacological intervention against such pathological conditions.
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Cite this article as:
Pathophysiological Role of Mitochondrial Potassium Channels and their Modulation by Drugs, Current Medicinal Chemistry 2018; 25 (23) . https://dx.doi.org/10.2174/0929867324666171012115300
DOI https://dx.doi.org/10.2174/0929867324666171012115300 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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