Impaired iron homeostasis in Parkinson’s disease

  • K. L. Double
  • M. Gerlach
  • M.B.H. Youdim
  • P. Riederer
Conference paper


Despite physiological systems designed to achieve iron homeostasis, increased concentrations of brain iron have been demonstrated in a range of neurodegenerative diseases. These including the parkinsonian syndromes, the trinucleotide repeat disorders and the dementia syndromes. The increased brain iron is confined to those brain regions most affected by the degeneration characteristic of the particular disorder and is suggested to stimulate cell damage via oxidative mechanisms. Changes in central iron homeostasis have been most closely investigated in PD, as this disorder is well characterised both clinically and pathologically. PD is associated with a significant increase in iron in the degenerating substantia nigra (SN) and is measureable in living PD patients and in post-mortem brain. This increase, however, occurs only in the advanced stages of the disease, suggesting that this phenonoma may be a secondary, rather than a primary initiating event, a hypothesis also supported by evidence from animal experiments. The source of the increased iron is unknown but a variety of changes in iron homeostasis have been identified in PD, both in the brain and in the periphery. The possibility that an increased amount of iron may be transported into the SN is supported by data demonstrating that one form of the iron-binding glycoprotein transferrin family, lactotransferrin, is increased in surviving neurons in the SN in the PD brain and that this change is associated with increased numbers of lactotransferrin receptors on neurons and microvessels in the parkinsonian SN. These changes could represent one mechanism by which iron might concentrate within the PD SN. Alternatively, the measured increased in iron might result from a redistribution of ferritin iron stores. Ferritin is located in glial cells while the degenerating neurons do not stain positive for ferritin.


Substantia Nigra Dementia With Lewy Body Progressive Supranuclear Palsy Iron Homeostasis Brain Iron 
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Copyright information

© Springer-Verlag Wien 2000

Authors and Affiliations

  • K. L. Double
    • 1
  • M. Gerlach
  • M.B.H. Youdim
    • 2
  • P. Riederer
    • 3
  1. 1.Prince of Wales Medical Research InstituteSydneyAustralia
  2. 2.Clinic and Policlinic of Psychiatry and PsychotherapyUniversity of WürzburgWürzburgGermany
  3. 3.Department of Pharmacology, BRappoport Faculty of Medicine, Eve Topf Neurodegenerative and National Parkinson Foundation CentersTechnion, HaifaIsrael

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