Brain iron metabolism

Alterations in brain iron metabolism have been reported, resulting in increased iron accumulation in Huntington s disease. This was particularly the case in basal ganglia from patients with HD compared to normal controls. In studies in embryonic stem cells, huntingtin was found to be iron-regulated, essential for the function of normal nuclear and perinuclear organelles and to be involved in the regulation of iron homeostasis. 

Sipe JC, Lee P, Beutler E. Brain iron metabolism and neurodegenerative disorders. Dev Neurosci 2002 24 188-96. 

Youdim, M.B.H. (1985) Brain iron metabolism biochemical and behavioural aspects in relation to dopaminergic neurotransmission. In A. Lajtha (Ed.), Handbook of Neurochemistry, Vol. 10, Plenum Press, New York, pp. 731-765. 

An inevitable consequence of ageing is an elevation of brain iron in specific brain regions, e.g. in the putamen, motor cortex, pre-frontal cortex, sensory cortex and thalamus, localized within H- and L-ferritin and neuromelanin with no apparent adverse effect. However, ill-placed excessive amounts of iron in specific brain cellular constituents, such as mitochondria or in specific regions brain, e.g. in the substantia nigra and lateral globus pallidus, will lead to neurodegenerative diseases (Friedreich s ataxia and Parkinson s disease (PD), respectively). We discuss here a few of the examples of the involvement of iron in neurodegenerative diseases. From more on iron metabolism see Crichton, 2001. 

There is increasing evidence that iron is involved in several neurodegenera-tive diseases. Conditions such as neuroferritinopathy and Friedreich ataxia are associated with mutations in genes that encode proteins that are involved in iron metabolism. As the brain ages, iron accumulates in regions that are affected in AD and PD. High concentrations of reactive iron can increase... 

Copper is required for the activity of enzymes associated with iron metabolism, elastin and collagen formation, melanin production and the integrity of the central nervous system. It is required with iron for normal red blood cell formation. Copper is also required for bone formation, brain cell and spinal cord structure, the immune response and feather development and pigmentation. A deficiency of copper leads to poor iron mobilization, abnormal... 

With this objective in mind, we examined the effects of Al accumulated in brain cells on the iron metabolism using primary cultures from the fetal rat cerebral cortex. To examine the influence of Al on the iron metabolism, the... 

The effect of administration of benzene on iron metabolism was investigated by giving 0.5 mL/kg intraperitoneally or 1 mL/kg subcutaneously to female rats for 10 consecutive days (Ahmad et al. 1994). Serum from benzene-treated female rats offered less protection against iron-catalyzed lipid peroxidation of brain tissue than the serum of control female rats. Serum iron concentration and total iron binding capacity did not exhibit any significant change after benzene administration. Iron saturation of transferritin was not affected by benzene. 

If iron mobilization is dependent on Cp, shouldn t there be a disturbance in iron metabolism, perhaps resembling copper deficiency, in Wilson s disease This is a disorder characterized by low plasma Cp and the accumulation of copper in the liver and brain. It is treated by eliminating copper from the diet and/or removing copper by administering penicillamine. However, the evidence to support a concomitant upset in iron utilization is tenuous. There is one recent paper by O Reilly et al. (51) in which eight patients with Wilson s disease were reported to have iron deficiency or low plasma iron or both, sometimes associated with anemia. Most of these subjects had low or low-normal levels of transferrin. One mitigating factor is that the size of the spleen in Wilson s disease is almost doubled and this may permit a more rapid turnover of plasma iron despite the low plasma ferroxidase activity. 

Chen Q, Beard JL, Jones BC. 1995. Abnormal rat brain monoamine metabolism in iron deficiency anemia. J Nutr Biochem 6 486M93. 

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