Data_Sheet_1_Proteomic Approaches to Study Cysteine Oxidation: Applications in Neurodegenerative Diseases.PDF

Oxidative stress appears to be a key feature of many neurodegenerative diseases either as a cause or consequence of disease. A range of molecules are subject to oxidation, but in particular, proteins are an important target and measure of oxidative stress. Proteins are subject to a range of oxidative modifications at reactive cysteine residues, and depending on the level of oxidative stress, these modifications may be reversible or irreversible. A range of experimental approaches has been developed to characterize cysteine oxidation of proteins. In particular, mass spectrometry-based proteomic methods have emerged as a powerful means to identify and quantify cysteine oxidation sites on a proteome scale; however, their application to study neurodegenerative diseases is limited to date. Here we provide a guide to these approaches and highlight the under-exploited utility of these methods to measure oxidative stress in neurodegenerative diseases for biomarker discovery, target engagement and to understand disease mechanisms.

氧化应激（Oxidative stress）似乎是诸多神经退行性疾病的核心特征之一，既可作为疾病的诱因，也可作为疾病的继发结果。诸多分子均可发生氧化修饰，而蛋白质尤为关键：它既是氧化应激的重要作用靶点，也是氧化应激水平的衡量标志物。蛋白质可在反应性半胱氨酸残基上发生多种氧化修饰，且根据氧化应激程度的差异，这类修饰可表现为可逆或不可逆状态。目前已开发出多种实验手段，用于表征蛋白质的半胱氨酸氧化状态。其中，基于质谱的蛋白质组学方法已成为在全蛋白质组范围内鉴定并定量半胱氨酸氧化位点的强有力工具；但迄今为止，这类方法在神经退行性疾病研究中的应用仍相对有限。本文将对这类方法进行系统梳理，并着重强调这类方法在神经退行性疾病研究中尚未被充分发掘的应用潜力：可用于氧化应激水平检测、生物标志物筛选、靶点结合验证以及疾病机制阐释。