摘要
背景:越来越多人认识到金属离子dyshomeostasis在衰老相关的神经退行性疾病的发展中起着至关重要的作用。大脑中的金属运输与调节神经元中金属吸收和流出的蛋白质有关。取决于金属蛋白复合物的特定结合特征,可能发生不同的途径。特别是,铜,锌和铁被认为会影响参与神经变性的蛋白质(例如Aβ和α-突触核蛋白)的生物化学,以及那些在神经元发育和效率(神经营养蛋白)中起关键作用的生物化学。目前基于肽的药物的应用在不同的病理学中是普遍的,但由于蛋白水解和其他缺点导致的体内短寿命仍然限制了它们的使用。 方法:进行关于现有技术的结构化搜索:i)用于获得模拟与神经元存活有关的蛋白质的金属结合活性的肽的肽模拟物方法,ii)基于肽的纳米结构,作为组织工程和基底中有前景的生物材料用于神经突生长和突触形成。 结果:综述了金属结合肽和肽纳米结构在神经退行性疾病治疗中的最新进展,显示金属离子相互作用可能影响神经退行性疾病中涉及的不同蛋白质的结构和生物学性质。 结论:本综述提供了一个关于能够模拟整个蛋白质的某些生物功能活性的肽的调查,例如与金属离子的结合特征,从而突出了它们作为新的更有效的治疗剂的潜力。将这些多肽纳入多功能纳米平台可以成为开发生物材料支架和纳米医学应用的智能途径。
关键词: 阿尔茨海默氏病,帕金森病,金属抑制,自组装,治疗性肽,血脑屏障,纳米颗粒,支持的脂质双层。
Current Medicinal Chemistry
Title:Peptides and their Metal Complexes in Neurodegenerative Diseases: from Structural Studies to Nanomedicine Prospects
Volume: 25 Issue: 6
关键词: 阿尔茨海默氏病,帕金森病,金属抑制,自组装,治疗性肽,血脑屏障,纳米颗粒,支持的脂质双层。
摘要: Background: The metal ions dyshomeostasis is increasingly recognized to play a crucial role in the development of aging-related neurodegenerative diseases. Metal trafficking in the brain is related to proteins regulating both uptake and efflux of metals in neurons. Different pathways may occur, depending on specific binding features of metallo-protein complexes. In particular, copper, zinc and iron are recognized to influence the biochemistry of proteins involved in neurodegeneration (for instance Aβ and α-synuclein), as well as those playing a crucial role in neuronal development and efficiency (neurotrophins). Nowadays the application of peptide-based drugs is widespread for different pathologies, but the short lifetime in vivo due to proteolysis and other shortcomings still limit their use.
Methods: A structured search was performed about the state of the art on: i) peptidomimetic approaches used to obtain peptides mimicking the metal binding activities of proteins involved in neurons survival, ii) peptide-based nanostructures, as promising biomaterials in tissue engineering and substrates for neurites outgrowth and synapses formation.
Results: Recent developments on metal-binding peptides and peptide nanostructures for therapeutic application in neurodegenerative diseases are reviewed, showing as metal ions interaction may affect structural and biological properties of different proteins involved in neurodegenerative diseases.
Conclusion: This review provides a survey on peptides able to mimic some biofunctional activities of the whole protein, e.g., the binding features to metal ions, thus highlighting their promising potentialities as new, more effective, therapeutics. The integration of such peptides into multifunctional nanoplatforms can be a smart route for the development of biomaterials scaffolds and nanomedicine applications.
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Peptides and their Metal Complexes in Neurodegenerative Diseases: from Structural Studies to Nanomedicine Prospects, Current Medicinal Chemistry 2018; 25 (6) . https://dx.doi.org/10.2174/0929867324666171026163144
DOI https://dx.doi.org/10.2174/0929867324666171026163144 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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