Functional roles of transferrin in the brain

Background: Transferrin is synthesized in the brain by choroid plexus and oligodendrocytes, but only that in the choroid plexus is secreted. Transferrin is a major iron delivery protein to the brain, but the amount transcytosed across the brain microvasculature is minimal. Transferrin is the major source of iron delivery to neurons. It may deliver iron to immature oligodendrocytes but this trophic effect declines over time while iron requirements for maintaining myelination continue. Finally, transferrin may play an important role in neurodegenerative diseases through its ability to mobilize iron. Scope of review: The role of transferrin in maintaining brain iron homeostasis and the mechanism by which it enters the brain and delivers iron will be discussed. Its relevance to neurological disorders will also be addressed. Major conclusions: Transferrin is the major iron delivery protein for neurons and the microvasculature, but has a limited role for glial cells. The main source of transferrin in the brain is likely from the choroid plexus although the concentration of transferrin at any given time in the brain includes that synthesized in oligodendrocytes. Little is known about brain iron egress or the role of transferrin in this process. General significance: Neuron survival requires iron, which is predominantly delivered by transferrin. The concentration of transferrin in the cerebrospinal fluid is reflective of brain iron availability and can function as a biomarker in disease. Accumulation of iron in the brain contributes to neurodegenerative processes, thus an understanding of the role that transferrin plays in regulating brain iron homeostasis is essential. This article is part of a Special Issue entitled Transferrins: Molecular mechanisms of iron transport and disorders.