Abstract
Reactive oxygen species and reactive nitrogen species (RONS) are by-products of aerobic metabolism. RONS trigger a signaling cascade that can be transduced through oxidation-reduction (redox)-based post-translational modifications (redox PTMs) of protein thiols. This redox signaling is essential for normal cellular physiology and coordinately regulates the function of redox-sensitive proteins. It plays a particularly important role in the brain, which is a major producer of RONS. Aberrant redox PTMs of protein thiols can impair protein function and are associated with several diseases. This mini review article aims to evaluate the role of redox PTMs of protein thiols, in particular S-nitrosation, in brain aging, and in neurodegenerative diseases. It also discusses the potential of using redox-based therapeutic approaches for neurodegenerative conditions.
Highlights
Reactive oxygen species and reactive nitrogen species (RONS) are essential signaling molecules produced by the aerobic metabolism (Friedman, 2010a; Finkel, 2011; Sbodio et al, 2019)
A recent study has mapped the oxidized Cys residues landscape in ten different tissues from wild-type mice using a highly sensitive and specific approach and has shown that oxidized Cys residues were detected in almost half of all proteins in all tissues tested suggesting that redox post-translational modifications (PTMs) of protein thiols is a widely used signaling mechanism in normal cellular physiology (Go et al, 2011; Xiao et al, 2020)
Redox PTMs of protein thiols play an important role in normal cell physiology, brain aging, and in the pathophysiology of several neurodegenerative conditions, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS)
Summary
Reactive oxygen species and reactive nitrogen species (RONS) are essential signaling molecules produced by the aerobic metabolism (Friedman, 2010a; Finkel, 2011; Sbodio et al, 2019). One essential route to transduce RONS signaling is through oxidation-reduction (redox)-based post-translational modifications (PTMs) of proteins (Stadtman, 1988; Stadtman and Levine, 2003; Finkel, 2011; Santos and Lindner, 2017). The mammalian brain is metabolically very active and is a major producer of RONS (Colton and Gilbert, 2002; Friedman, 2010a,b). RONS-dependent redox signaling is important in the normal physiology of the brain (Colton and Gilbert, 2002; Beckhauser et al, 2016). O/N stresses are active contributing factors to the pathophysiological mechanisms underpinning neurodegenerative conditions including Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS; Friedman, 2010a,b; Kim et al, 2015; Liu et al, 2017; Sbodio et al, 2019)
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