Systemic iron metabolism: A review and implications for brain iron metabolism

Mammalian cells and organisms coordinate to regulate expression of numerous proteins involved in the uptake, sequestration, and export of iron. When c ells in the systemic circulation are depleted of iron, they increase synthe sis of the transferrin receptor and decrease synthesis of the iron sequestr ation protein, ferritin. In iron-depleted animals, expression of duodenal i ron transporters markedly increases and intestinal iron uptake increases ac cordingly. The major proteins of iron metabolism in the systemic circulatio n are also expressed in the central nervous system. However, the mechanisms by which iron is transported and distributed throughout the central nervou s system are not well understood. Iron accumulation in specific regions of the brain is observed in several neurodegenerative diseases. It is likely t hat misregulation of iron metabolism is important in the pathophysiology of several human neurodegenerative diseases. (C) 2001 by Elsevier Science Inc . All rights reserved.