Proteomic approaches to quantify cysteine reversible modifications in aging and neurodegenerative diseases.
Cysteine is a highly reactive amino acid and is subject to a variety of reversible post-translational modifications (PTMs), including nitrosylation, glutathionylation, palmitoylation, as well as formation of sulfenic acid and disulfides. These modifications are not only involved in normal biological activities, such as enzymatic catalysis, redox signaling, and cellular homeostasis, but can also be the result of oxidative damage. Especially in aging and neurodegenerative diseases, oxidative stress leads to aberrant cysteine oxidations that affect protein structure and function leading to neurodegeneration as well as other detrimental effects. Methods that can identify cysteine modifications by type, including the site of modification, as well as the relative stoichiometry of the modification can be very helpful for understanding the role of the thiol proteome and redox homeostasis in the context of disease. Cysteine reversible modifications however, are challenging to investigate as they are low abundant, diverse, and labile especially under endogenous conditions. Thanks to the development of redox proteomic approaches, large-scale quantification of cysteine reversible modifications is possible. These approaches cover a range of strategies to enrich, identify, and quantify cysteine reversible modifications from biological samples. This review will focus on nongel-based redox proteomics workflows that give quantitative information about cysteine PTMs and highlight how these strategies have been useful for investigating the redox thiol proteome in aging and neurodegenerative diseases.
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA.
Liqing
L
Gu
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA.
Renã A S
RA
Robinson
D000375:Aging / Q000378:metabolism*; D000818:Animals; D003545:Cysteine / Q000378:metabolism*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D010084:Oxidation-Reduction; D011499:Protein Processing, Post-Translational; D040901:Proteomics / Q000379:methods*
D003545:Cysteine
Aging; Alzheimer's disease; Cysteine; Mass spectrometry; Neurodegenerative diseases; Oxidation; Quantitative proteomics; Redox proteomics; Reversible PTMs; Review
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