Any old iron?

Abstract

Listen

Translate article

‘Stop all your work’, he said. ‘Clear away all those tasks you have started … give this your immediate attention.’ [Virgil, Before the current era: 29–19 (Ahl, 2007)] Iron is central to mammalian biochemistry and physiology. Its role extends from the haemoglobin molecule with its haem iron groups responsible for transporting oxygen, to the iron sulphur clusters found in mitochondrial respiratory chain enzymes that provide energy for cellular maintenance and metabolism (Crichton et al. , 2002). Much has been learned about the peripheral changes that occur following altered body iron status either in deficiency, for example anaemia, or overload, such as haemochromatosis, but we are only now beginning to understand the regulation of iron in the nervous system. The brain is uniquely susceptible to perturbations in iron metabolism due to the high demand for energy to support neuronal activity (Morris et al. , 1992 a ; Kann et al. , 2011); and the relative absence of neuronal cell division leaves neurons open to attack by iron-mediated free radicals. Iron is also required for monoamine metabolism since tryptophan and tyrosine hydroxylase, and monoamine oxygenase require iron as a cofactor; this places iron centrally within neurotransmitter systems needed for cognition, attention and motivation (Youdim and Yehuda, 2000). Iron shows complex mechanisms of uptake and distribution in the brain with access from the periphery relying on expression of the iron transport protein transferrin and its receptor at the blood–brain barrier (Taylor et al. , 1991; Morris et al. , 1992 d ). At the blood–brain barrier, iron is removed from transferrin, which recycles back to the periphery; iron is then transferred to the abluminal side of the barrier where astrocytes facilitate its further transport (Crowe and Morgan, 1992; Moos et al. , 2006, 2007). In the adult brain, iron uptake …