ABSTRACT
Mitochondrial dysfunction and oxidative stress are increasingly implicated in the pathophysiology of schizophrenia. The brain is the body’s highest energy consumer, and the glutathione system is the brain’s dominant free radical scavenger. In the current paper, we review the evidence of central and peripheral nervous system anomalies in the oxidative defences of individuals with schizophrenia, principally involving the glutathione system. This is reflected by evidence of the manifold consequences of oxidative stress that include lipid peroxidation, protein carboxylation, DNA damage and apoptosis – all potentially part of the process of neuroprogression in the disorder. Importantly, oxidative stress is amenable to intervention. We consider the clinical potential of some possible interventions that help reduce oxidative stress, via augmentation of the glutathione system, particularly N-acetyl cysteine. We argue that a better understanding of the mechanisms and pathways underlying oxidative stress will assist in developing the therapeutic potential of this area.
The brain is, weight for weight, the most metabolically active tissue in the body and generates a high load of reactive oxygen moieties. This burden is increased by a number of factors, including the oxidative potential of monoamines such as dopamine and excitatory neurotransmitters such as glutamate, as well as the vulnerability of the brain’s lipid components to oxidation.1 Although free radicals are important for a number of physiological functions, such as mitosis and cellular signalling,2 if their metabolism is dysregulated, they have the potential to damage most of the contents of the cell, including lipids via peroxidation, protein via carboxylation and nucleic acids via oxidative damage.
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