Abstract
Brain iron is an essential nutrient for multiple functions, including gene expression, DNA synthesis, neurotransmission, myelination, oxygen transport, storage and activation, mitochondrial electron transport, numerous important metabolic processes and cofactor for several key enzymes of neurotransmitter biosynthesis. On the other hand, many investigators, among them the late Mark Smith, who was a pioneer neuroscientist and prominent investigator with regards to brain oxidative stress (OS) and iron in Alzheimer's disease, have identified iron as an highly reactive element that can promote OS processes within the brain and might increase the toxicity of environmental or endogenous toxins. It is suggested that iron accumulation in the brain is capable of initiating free-radical reactions, which subsequently induce progressive loss of neurons, followed by a decrement in neuronal function characteristic of the ageing process. Indeed, it has become apparent that iron progressively accumulates in the brain as a function of age and that iron-induced OS can cause neurodegeneration. Chelation therapy was previously introduced as a novel therapy concept and rationale for the development of metal-binding drugs for neurodegeneration. The present review will discuss the involvement of dysregulation of brain iron homeostasis in the ageing process, addressing the potential importance of iron chelating therapeutic approaches.