AUTHOR=Pham Trong Khoa, Buczek Weronika A., Mead Richard J., Shaw Pamela J., Collins Mark O. TITLE=Proteomic Approaches to Study Cysteine Oxidation: Applications in Neurodegenerative Diseases JOURNAL=Frontiers in Molecular Neuroscience VOLUME=14 YEAR=2021 URL=https://www.frontiersin.org/articles/10.3389/fnmol.2021.678837 DOI=10.3389/fnmol.2021.678837 ISSN=1662-5099 ABSTRACT=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.