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The cellular thiol pool represents the collective concentration of sulfhydryl-containing molecules within a cell, primarily composed of low-molecular-weight (LMW) thiols like glutathione (GSH) and protein-based cysteine residues (NIH, 2008; Portland Press, 2021). This pool is critical for maintaining intracellular redox homeostasis, protecting cells against oxidative damage by scavenging reactive oxygen species (ROS) and detoxifying electrophilic xenobiotics (MDPI, 2021; NIH, 2020). In many diseases, particularly cancer, the thiol pool is often upregulated to provide a survival advantage and resistance against pro-oxidant therapies, making its depletion a viable strategy for sensitizing tumors (NIH, 1985; National Jewish Health, 2023). Conversely, in neurodegenerative and cardiovascular diseases, replenishing the thiol pool with antioxidants or precursors like N-acetylcysteine is explored to mitigate oxidative stress-induced damage (NIH, 2007; NIH, 2020). Pharmacological intervention typically involves either direct supplementation, inhibition of thiol synthesis enzymes like gamma-glutamylcysteine synthetase, or the use of electrophilic drugs that conjugate with and deplete these molecules (NIH, 2008; MDPI, 2021).
Modulation of the cellular redox state through the replenishment or depletion of sulfhydryl-containing molecules, thereby affecting antioxidant capacity and electrophile detoxification (NIH, 2020; MDPI, 2021).
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