Abstract
Hydrogen sulfide (H2S), originally considered a toxic gas, is now a recognized gasotransmitter. Numerous studies have revealed the role of H2S as a redox signaling molecule that controls important physiological/pathophysiological functions. The underlying mechanism postulated to serve as an explanation of these effects is protein persulfidation (P-SSH, also known as S-sulfhydration), an oxidative posttranslational modification of cysteine thiols. Protein persulfidation has remained understudied due to its instability and chemical reactivity similar to other cysteine modifications, making it very difficult to selectively label. Recent developments of persulfide labeling techniques have started unraveling the role of this modification in (patho)physiology. PSSH levels are important for the cellular defense against oxidative injury, albeit they decrease with aging, leaving proteins vulnerable to oxidative damage. Aging is one of the main risk factors for many neurodegenerative diseases. Persulfidation has been shown to be dysregulated in Parkinson's, Alzheimer's, Huntington's disease, and Spinocerebellar ataxia 3. This article reviews the latest discoveries that link protein persulfidation, aging and neurodegeneration, and provides future directions for this research field that could result in development of targeted drug design.
Highlights
Hydrogen sulfide (H2S) is a small colorless gas that has sparked large controversy over the past two decades
The recognition of the physiological importance of H2S started to emerge from the first report by Abe and Kimura, identifying that H2S is a neurological modulator in the brain (Abe and Kimura, 1996), stimulating a productive two decades of research
The lack of H2S producing enzymes in flies, worms, and rodents abolishes the positive effects of dietary restriction (DR), while the overexpression of these enzymes mimic the effects of DR without any dietary intervention (Kabil et al, 2011; Hine et al, 2015)
Summary
Leibniz-Institut für Analytische Wissenschaften – ISAS - e.V., Dortmund, Germany. The underlying mechanism postulated to serve as an explanation of these effects is protein persulfidation (P-SSH, known as S-sulfhydration), an oxidative posttranslational modification of cysteine thiols. Protein persulfidation has remained understudied due to its instability and chemical reactivity similar to other cysteine modifications, making it very difficult to selectively label. Recent developments of persulfide labeling techniques have started unraveling the role of this modification in (patho)physiology. This article reviews the latest discoveries that link protein persulfidation, aging and neurodegeneration, and provides future directions for this research field that could result in development of targeted drug design
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