摘要
背景:寻找治疗神经退行性疾病的新药物的迫切性迫在眉睫大量的综述详尽地描述了神经退行性疾病如阿尔茨海默氏病(AD)和帕金森病(PD)的分子或临床方面。相反,报告概述了已知药物如何用于其他疾病也可能是有效的,因为神经退行性疾病中的治疗剂报道较少。本综述重点讨论了一些铜(II)螯合分子在神经退行性疾病中作为潜在药物候选物的当前用途。 方法:从金属失调和金属失控与AD发病之间存在的众所周知的有害关系出发,我们调查了文献报道的实验性工作,其涉及金属螯合药物在神经退行性疾病领域的重新定位审查的论文从常规文献中检索,其选择仅限于那些描述与神经保护相关的生物分子方面的论文。特别是,我们强调了所选药物的铜(II)配位能力。 结果:。已知铜与锌和铁一起在调节神经元功能中起关键作用铜稳态的变化对几种神经退行性疾病至关重要本综述所包含的研究可能提供目前用于治疗神经退行性疾病的铜(II)螯合药重新使用的策略的综述。从氯碘羟喹再利用的示例性案例开始,我们讨论了挑战和其他金属螯合药物的再利用可能提供的机会(例如PBT -2,二甲双胍和环二肽)治疗神经退行性疾病。 结论:为了提高药物重新定位的成功率,仍需要对其分子机制和疗效进行全面的研究。目前的评论认为,药物重新使用比起药物发现具有显着的优势。试验。神经退行性疾病中有希望的候选药物可以由铜螯合类药物代表,前提是足够的细节介绍其作用机制可用于鼓励进一步的研究和临床试验。
关键词: Clioquinol,二甲双胍,铜,神经退行性疾病,药物再利用,金属抑制,环二肽。
Current Medicinal Chemistry
Title:Repurposing of Copper(II)-chelating Drugs for the Treatment of Neurodegenerative Diseases
Volume: 25 Issue: 4
关键词: Clioquinol,二甲双胍,铜,神经退行性疾病,药物再利用,金属抑制,环二肽。
摘要: Background: There is mounting urgency to find new drugs for the treatment of neurodegenerative disorders. A large number of reviews have exhaustively described either the molecular or clinical aspects of neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's (PD). Conversely, reports outlining how known drugs in use for other diseases can also be effective as therapeutic agents in neurodegenerative diseases are less reported. This review focuses on the current uses of some copper(II) chelating molecules as potential drug candidates in neurodegeneration.
Methods: Starting from the well-known harmful relationships existing between the dyshomeostasis and mis-management of metals and AD onset, we surveyed the experimental work reported in the literature, which deals with the repositioning of metal-chelating drugs in the field of neurodegenerative diseases. The reviewed papers were retrieved from common literature and their selection was limited to those describing the biomolecular aspects associated with neuroprotection. In particular, we emphasized the copper(II) coordination abilities of the selected drugs.
Results: Copper, together with zinc and iron, are known to play a key role in regulating neuronal functions. Changes in copper homeostasis are crucial for several neurodegenerative disorders. The studies included in this review may provide an overview on the current strategies aimed at repurposing copper (II) chelating drugs for the treatment of neurodegenerative disorders. Starting from the exemplary case of clioquinol repurposing, we discuss the challenge and the opportunities that repurposing of other metal-chelating drugs may provide (e.g. PBT-2, metformin and cyclodipeptides) in the treatment of neurodegenerative disease.
Conclusions: In order to improve the success rate of drug repositioning, comprehensive studies on the molecular mechanism and therapeutic efficacy are still required. The present review upholds that drug repurposing makes significant advantages over drug discovery since repositioned drugs had already passed the safety and toxicity tests. Promising drug candidates in neurodegenerative diseases may be represented by copper chelating classes of drugs, provided that sufficient details on their mechanism of action are available to encourage further investigations and clinical trials.
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Cite this article as:
Repurposing of Copper(II)-chelating Drugs for the Treatment of Neurodegenerative Diseases, Current Medicinal Chemistry 2018; 25 (4) . https://dx.doi.org/10.2174/0929867324666170518094404
DOI https://dx.doi.org/10.2174/0929867324666170518094404 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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