Iron Homeostasis in the CNS: An Overview of the Pathological Consequences of Iron Metabolism Disruption

Abstract

Iron homeostasis disruption has increasingly been implicated in various neurological disorders. In this review, we present an overview of our current understanding of iron metabolism in the central nervous system. We examine the consequences of both iron accumulation and deficiency in various disease contexts including neurodegenerative, neurodevelopmental, and neuropsychological disorders. The history of animal models of iron metabolism misregulation is also discussed followed by a comparison of three patients with a newly discovered neurodegenerative disorder caused by mutations in iron regulatory protein 2.

Keywords: iron accumulation; iron deficiency; iron homeostasis; iron metabolism; iron regulatory proteins; neurodegeneration.

Figure 1

Perls’ DAB stain (left) and amino cupric silver stain (right) of WT (top), Irp2^−/− (middle), and Irp1^+/−Irp2^−/− (bottom) mouse cerebellum sections showing a dose-dependent effect of IRP ablation on iron accumulation in white matter (yellow) and axon degeneration (black strands). Abbreviations: CDN—cerebellar deep nuclei, W—white matter, G—granular cell layer, P—Purkinje cell layer, M—molecular layer. Modified with permission from ref. [1] 2015 Elsevier.