Oxidative stress and neuronal mitochondrial function. Factors dictating susceptibility

Abstract

Oxidative stress and loss of neuronal mitochondrial function, particularly at the level of cytochrome oxidase has been implicated in the neurodegenerative process. Cell culture studies have revealed that neurones, in comparison to astrocytes, may be particularly susceptible, when cultured alone, to the action of oxidising species such as nitric oxide and peroxynitrite. An important factor in dictating such susceptibility appears to be the intracellular level of the antioxidant, glutathione (GSH). Whilst the coculture of neurones with nitric oxide generating astrocytes leads to neuronal mitochondrial damage, such damage appears to be initially limited due to the up‐regulation of neuronal GSH status by astrocytes. Other factors that may dictate the susceptibility of brain cell types to oxidative stress include the ability of cells to up‐regulate glycolysis in the face of mitochondrial damage and cellular ubiquinone availability.