Iron storage and transport markers in Parkinson’s disease and MPTP-treated mice
The regulation of neuronal iron is necessary for the synthesis of iron containing cytochromes and to prevent damage from free radicals by iron-oxygen interactions. We have shown that transferrin receptors are elevated over the substantia nigra in the human and rat brain (Mash et al., 1990) and are depleted concomitantly with dopaminergic terminals in the MPTP-treated mouse striatum (Mash et al., 1991). Given the iron dependency for both synthetic and degradative enzyme activities, dopaminergic neurons may express transferrin receptors on their cell surface to facilitate the uptake of iron bound to transferrin. If the intracellular iron pool is regulated by receptor-mediated transferrin uptake, then an up-regulation of transferrin receptor number may play a role in the pathogenesis of nigral cell damage in Parkinson’s disease. Early in the disease process, surviving dopaminergic neurons may increase the number of transferrin receptors in order to meet the increased metabolic demand associated with compensatory changes in dopamine synthesis and turnover. The uptake of ferrotransferrin by dopaminergic neurons may result in a progressive elevation in the cellular iron load that exceeds the regulatory capacity for increased ferritin expression in the aging brain.
KeywordsSubstantia Nigra Progressive Supranuclear Palsy Iron Storage Transferrin Receptor Brain Iron
Unable to display preview. Download preview PDF.
- Dexter D, Wells F, Lees A (1987) Increased nigral iron content in post-mortem parkinsonian brain. Lancet ii: 1219–1220Google Scholar
- Donaldson J, Barbeau A (1985) Manganese neurotoxicity: possible clues to the etiology of human brain disorders. In: Neurology and neurobiology, vol 15. Metal ions in neurology and psychiatry. Liss, New York, pp 259–285Google Scholar
- Dreosti I, Smith R (1983) Neurobiology of trace elements, vol 1. Humana, Clifton NJ, pp 269–291Google Scholar
- Götz M, Freyberger A, Riederer P (1990) Oxidative stress: a role in the pathogenesis of Parkinson’s disease. J Neural Transm [Suppl] 29: 241–249Google Scholar
- Halliwell B (1987) Oxidants and human disease: some new concepts. Fed Am Soc Exp Biol 892: 358–364Google Scholar
- Hill J (1988) Brain iron: neurochemical and behavioral aspects. Taylor and Francis, London, pp 1–24Google Scholar
- Jefferies W, Brandon M, Hunt 5, Williams A, Gatters K, Masons D (1984) Transferrin receptor on endothelium of brain capillaries. Nature 312: 162–163 Joshi JGoogle Scholar
- Norfray J, Couch J, Elble R, Good D, Manyam B, Patrick J (1988) Visualization of brain iron by mid-field MR. Am J Neurorad 9: 77–82Google Scholar
- Ricaurte G, Langston J, Delanney L, Irwin I, Peroutka S, Forno L (1986) Fate of nigrostriatal neurons in young mature mice given 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine: a neurochemical and morphological reassessment. Brain Res 375: 117–124Google Scholar
- Rutledge J, Hilal S, Silver A, Defendini R, Fahn S (1987) Study of movement disorders and brain iron by MR. Am J Neurorad 8: 397–411Google Scholar