Cysteine Metabolism in Neuronal Redox Homeostasis

• Published in: Trends in pharmacological sciences (Regular ed.) 2018-05, Vol.39 (5), p.513-524
• Main Authors: Paul, Bindu D., Sbodio, Juan I., Snyder, Solomon H.
• Format: Article
• Language: English
• Subjects: Animals; ATF4; Autophagy; cysteine; Cysteine - biosynthesis; Cysteine - metabolism; Glutathione - metabolism; Homeostasis; Humans; Huntington’s disease; neurodegeneration; Neurodegenerative Diseases - metabolism; Neurons - metabolism; Oxidation-Reduction; Protein Processing, Post-Translational
• ISSN: 0165-6147; 1873-3735
• DOI: 10.1016/j.tips.2018.02.007

Besides its essential role in protein synthesis, cysteine plays vital roles in redox homeostasis, being a component of the major antioxidant glutathione (GSH) and a potent antioxidant by itself. In addition, cysteine undergoes a variety of post-translational modifications that modulate several physiological processes. It is becoming increasingly clear that redox-modulated events play important roles not only in peripheral tissues but also in the brain where cysteine disposition is central to these pathways. Dysregulated cysteine metabolism is associated with several neurodegenerative disorders. Accordingly, restoration of cysteine balance has therapeutic benefits. This review discusses metabolic signaling pathways pertaining to cysteine disposition in the brain under normal and pathological conditions, highlighting recent findings on cysteine metabolism during aging and in neurodegenerative conditions such as Huntington’s disease (HD) and molybdenum cofactor (MoCo) deficiency (MoCD) among others. Cysteine is a semi-essential amino acid that is a building block for not only protein synthesis but also the major antioxidant glutathione (GSH). Cysteine is the precursor for several sulfur-containing molecules such as the gaseous signaling molecule hydrogen sulfide, lanthionine, taurine, coenzyme A, and biotin. Although relatively scarce, cysteine undergoes the maximum number of post-translational modifications. Sulfhydration, the most recently discovered physiological modification, plays diverse roles in physiology ranging from response to inflammation to neuroprotection. Dysregulated cysteine and hydrogen sulfide metabolism is frequently encountered in several neurodegenerative disorders. Upregulating the reverse transsulfuration pathway, via which cysteine and hydrogen sulfide are produced, affords therapeutic benefits.