Iron deposits in the chronically inflamed central nervous system and contributes to neurodegeneration.
Neurodegenerative disorders are characterized by the presence of inflammation in areas with neuronal cell death and a regional increase in iron that exceeds what occurs during normal aging. The inflammatory process accompanying the neuronal degeneration involves glial cells of the central nervous system (CNS) and monocytes of the circulation that migrate into the CNS while transforming into phagocytic macrophages. This review outlines the possible mechanisms responsible for deposition of iron in neurodegenerative disorders with a main emphasis on how iron-containing monocytes may migrate into the CNS, transform into macrophages, and die out subsequently to their phagocytosis of damaged and dying neuronal cells. The dying macrophages may in turn release their iron, which enters the pool of labile iron to catalytically promote formation of free-radical-mediated stress and oxidative damage to adjacent cells, including neurons. Healthy neurons may also chronically acquire iron from the extracellular space as another principle mechanism for oxidative stress-mediated damage. Pharmacological handling of monocyte migration into the CNS combined with chelators that neutralize the effects of extracellular iron occurring due to the release from dying macrophages as well as intraneuronal chelation may denote good possibilities for reducing the deleterious consequences of iron deposition in the CNS.
Laboratory for Neurobiology, Biomedicine Group, Department of Health Science and Technology, Aalborg University, Fr. Bajers Vej 3B, 1.216, 9220, Aalborg East, Denmark.
Hjalte Holm
HH
Andersen
Kasper Bendix
KB
Johnsen
Torben
T
Moos
D002490:Central Nervous System / Q000378:metabolism*; D005293:Ferritins / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000737:chemistry / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress
D005609:Free Radicals; D007502:Iron Chelating Agents; D005293:Ferritins; D007501:Iron