Astrocytes and the regulation of cerebral cysteine/cystine redox potential: implications for cysteine neurotoxicity

The sulfur amino acid, cysteine plays an essential role in maintaining cellular redox potential and is a key constituent of the antioxidant, glutathione. Cysteine is highly reactive and readily oxidises to the disulfide form, cystine, producing oxygen radicals as a by-product. Extracellular oxidising conditions favour cystine, whereas cysteine is the dominant intracellular form of the amino acid.
In the brain, astrocytes control the extracellular thiol redox potential by actively taking up cystine and exporting cysteine. Particularly, astrocytes up-regulate the cysteine/cystine cycle in response to oxidative stress, which is essential for preventing damage to neuronal function arising from loss of redox balance.
Recent evidence shows that the extracellular cysteine/cystine redox state may have a significant role in a number of processes that affect synaptic activity, including signal transduction and receptor activation and may be implicated in a number of neurodegenerative diseases, for example Alzheimer’s and Parkinson’s.
This review charts recent developments in understanding the role of astrocytes in neuroprotection via management of the extracellular thiol redox potential in normal brain function and provides an up-to-date account of cysteine neurotoxicity and its significance in the aetiology of neurodegenerative disease.