N-acetyl-cysteine in Schizophrenia: Potential Role on the Sensitive Cysteine Proteome

Abstract

Background: N-acetyl-cysteine (NAC) has shown widespread utility in different psychiatric disorders, including a beneficial role in schizophrenic patients. Although the replenishment of glutathione and the antioxidant activity of NAC have been suggested as the mechanisms that improve such a wide range of disorders, no one seems to be sufficiently specific to explain these intriguing effects. A sensitive cysteine proteome is emerging as a functional and structural network of interconnected sensitive cysteine-containing proteins (SCCPs) that together with reactive species and the cysteine/glutathione cycles can regulate the bioenergetic metabolism, the redox homeostasis and the cellular growth, differentiation and survival, acting through different pathways that are regulated by the same thiol radical in cysteine residues. Objective: Since this sensitive cysteine network has been implicated in the pathogenesis of Parkinson and Alzheimer´s diseases, I have reviewed if the proteins that play a role in schizophrenia can be classified too as SCCPs. Results: I have revised the major proteins implicated in the physiopathology of schizophrenia searching for those proteins that are redox-regulated through sensitive cysteine thiols. Results show that the principal proteins playing a role in schizophrenia can be classified as SCCPs, suggesting that the sensitive cysteine proteome (cysteinet) is defective in this type of psychosis. Conclusion: The present review proposes that there is a deregulation of the sensitive cysteine proteome in schizophrenia as the consequence of a functional imbalance among different SCCPs, which play different functions in neurons and glial cells. In this context, the role of NAC to restore and prevent schizophrenic disorders is discussed.