Abstract:
Oxidation-reduction post-translational modifications (redox-PTMs) are chemical alterations to amino acids of proteins. Redox-PTMs participate in the regulation of protein conformation, localization and function, acting as signalling effectors that impact many essential biochemical processes in the cells. Crucially, the dysregulation of redox-PTMs of proteins has been implicated in the pathophysiology of numerous human diseases, including neurodegenerative diseases such as Alzheimer\'s disease and Parkinson\'s disease. This review aims to highlight the current gaps in knowledge in the field of redox-PTMs biology and to explore new methodological advances in proteomics and computational modelling that will pave the way for a better understanding of the role and therapeutic potential of redox-PTMs of proteins in neurodegenerative diseases. Here, we summarize the main types of redox-PTMs of proteins while providing examples of their occurrence in neurodegenerative diseases and an overview of the state-of-the-art methods used for their detection. We explore the potential of novel computational modelling approaches as essential tools to obtain insights into the precise role of redox-PTMs in regulating protein structure and function. We also discuss the complex crosstalk between various PTMs that occur in living cells. Finally, we argue that redox-PTMs of proteins could be used in the future as diagnosis and prognosis biomarkers for neurodegenerative diseases.
摘要:
氧化还原翻译后修饰(氧化还原-PTM)是蛋白质氨基酸的化学变化。氧化还原-PTM参与蛋白质构象的调节,本地化和功能,充当影响细胞中许多基本生化过程的信号效应物。至关重要的是,蛋白质的氧化还原-PTM的失调与许多人类疾病的病理生理学有关,包括神经退行性疾病,如阿尔茨海默病和帕金森病。这篇综述旨在强调氧化还原-PTMs生物学领域目前的知识空白,并探索蛋白质组学和计算模型的新方法进展,这将为更好地理解蛋白质的氧化还原-PTMs在神经退行性疾病中的作用和治疗潜力铺平道路。这里,我们总结了蛋白质的氧化还原-PTM的主要类型,同时提供了它们在神经退行性疾病中发生的例子,并概述了用于检测它们的最新方法。我们探索了新型计算建模方法作为必要工具的潜力,以了解氧化还原-PTM在调节蛋白质结构和功能中的精确作用。我们还讨论了在活细胞中发生的各种PTM之间的复杂串扰。最后,我们认为,蛋白质的氧化还原-PTMs将来可用作神经退行性疾病的诊断和预后生物标志物.