Brain iron transport

Biol Rev Camb Philos Soc. 2019 Oct;94(5):1672-1684. doi: 10.1111/brv.12521. Epub 2019 Jun 12.

Abstract

Brain iron is a crucial participant and regulator of normal physiological activity. However, excess iron is involved in the formation of free radicals, and has been associated with oxidative damage to neuronal and other brain cells. Abnormally high brain iron levels have been observed in various neurodegenerative diseases, including neurodegeneration with brain iron accumulation, Alzheimer's disease, Parkinson's disease and Huntington's disease. However, the key question of why iron levels increase in the relevant regions of the brain remains to be answered. A full understanding of the homeostatic mechanisms involved in brain iron transport and metabolism is therefore critical not only for elucidating the pathophysiological mechanisms responsible for excess iron accumulation in the brain but also for developing pharmacological interventions to disrupt the chain of pathological events occurring in these neurodegenerative diseases. Numerous studies have been conducted, but to date no effort to synthesize these studies and ideas into a systematic and coherent summary has been made, especially concerning iron transport across the luminal (apical) membrane of the capillary endothelium and the membranes of different brain cell types. Herein, we review key findings on brain iron transport, highlighting the mechanisms involved in iron transport across the luminal (apical) as well as the abluminal (basal) membrane of the blood-brain barrier, the blood-cerebrospinal fluid barrier, and iron uptake and release in neurons, oligodendrocytes, astrocytes and microglia within the brain. We offer suggestions for addressing the many important gaps in our understanding of this important topic, and provide new insights into the potential causes of abnormally increased iron levels in regions of the brain in neurodegenerative disorders.

Keywords: astrocyte; blood-brain barrier (BBB); blood-cerebrospinal fluid barrier (BCSFB); brain iron; iron uptake and release; microglia; neuron; oligodendrocyte.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Blood-Brain Barrier / metabolism*
  • Brain / metabolism*
  • Cerebrospinal Fluid / metabolism
  • Endothelium, Vascular / metabolism
  • Humans
  • Iron / metabolism*
  • Microglia / metabolism
  • Neurons / metabolism
  • Oligodendroglia / metabolism
  • Receptors, Transferrin / metabolism
  • Transferrin / metabolism

Substances

  • Receptors, Transferrin
  • Transferrin
  • Iron