Chapter

Parkinson’s Disease and Related Disorders

Volume 70 of the series Journal of Neural Transmission. Supplementa pp 133-142

Potential sources of increased iron in the substantia nigra of parkinsonian patients

  • M. GerlachAffiliated withLaboratory for Clinical Neurochemistry, Department of Child and Adolescence Psychiatry and Psychotherapy, University of Würzburg
  • , K. L. DoubleAffiliated withPrince of Wales Medical Research Institute
  • , M. B. H. YoudimAffiliated withEve Topf and National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases Research, and Department of Pharmacology, Technion-Faculty of Medicine
  • , P. RiedererAffiliated withLaboratory for Clinical Neurochemistry, Department of Psychiatry and Psychotherapy, and National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases Research, University of Würzburg

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Summary

Histopathological, biochemical and in vivo brain imaging techniques, such as magnetic resonance imaging and transcranial sonography, revealed a consistent increase of substantia nigra (SN) iron in Parkinson’s disease (PD). Increased iron deposits in the SN may have genetic and non-genetic causes. There are several rare movement disorders associated with neurodegeneration, and genetic abnormalities in iron regulation resulting in iron deposition in the brain. Non-genetic causes of increased SN iron may be the result of a disturbed or open blood-brain-barrier, local changes in the normal iron-regulatory systems, intraneuronal transportation of iron from iron-rich area into the SN and release of iron from intracellular iron storage molecules. Major iron stores are ferritin and haemosiderin in glial cells as well as neuromelanin in neurons. Age- and disease dependent overload of iron storage proteins may result in iron release upon reduction. Consequently, the low molecular weight chelatable iron complexes may trigger redox reactions leading to damage of biomolecules. Additionally, upon neurodegeneration there is strong microglial activation which can be another source of high iron concentrations in the brain.