New therapeutic strategies have emerged along with our understanding that disturbances of iron homeostasis, impaired proliferation of erythroid progenitor cells, and blunted erythropoietin response occur in anemia of chronic disease. This review discusses advances in our knowledge of the causes and management of the condition.

https://www.nejm.org/doi/pdf/10.1056/NEJMra041809

Anemia of Chronic Disease

Hypoferremia is a common response to systemic infections or generalized inflammatory disorders. In mouse models, the development of hypoferremia during inflammation requires hepcidin, an iron regulatory peptide hormone produced in the liver, but the inflammatory signals that regulate hepcidin are largely unknown. Our studies in human liver cell cultures, mice, and human volunteers indicate that IL-6 is the necessary and sufficient cytokine for the induction of hepcidin during inflammation and that the IL-6-hepcidin axis is responsible for the hypoferremia of inflammation.

/pdf/il-6-mediates-hypoferremia-of-inflammation-by-inducing-the-zpat5ma2tv.pdf

IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin

Balancing Acts: Molecular Control of Mammalian Iron Metabolism

There is increasing evidence that iron is involved in the mechanisms that underlie many neurodegenerative diseases. Conditions such as neuroferritinopathy and Friedreich ataxia are associated with mutations in genes that encode proteins that are involved in iron metabolism, and as the brain ages, iron accumulates in regions that are affected by Alzheimer's disease and Parkinson's disease. High concentrations of reactive iron can increase oxidative-stress induced neuronal vulnerability, and iron accumulation might increase the toxicity of environmental or endogenous toxins. By studying the accumulation and cellular distribution of iron during ageing, we should be able to increase our understanding of these neurodegenerative disorders and develop new therapeutic strategies.

/pdf/iron-brain-ageing-and-neurodegenerative-disorders-dj3psb0moe.pdf

Iron, brain ageing and neurodegenerative disorders

http://www.intrinsiclifesciences.com/wp-content/uploads/2013/08/The-iron-exporter-ferroportinSlc40a1-is-essential-for-iron-homeostasis.pdf

The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis

Juvenile hemochromatosis is an early-onset autosomal recessive disorder of iron overload resulting in cardiomyopathy, diabetes and hypogonadism that presents in the teens and early 20s (refs. 1,2). Juvenile hemochromatosis has previously been linked to the centromeric region of chromosome 1q (refs. 3–6), a region that is incomplete in the human genome assembly. Here we report the positional cloning of the locus associated with juvenile hemochromatosis and the identification of a new gene crucial to iron metabolism. We finely mapped the recombinant interval in families of Greek descent and identified multiple deleterious mutations in a transcription unit of previously unknown function (LOC148738), now called HFE2, whose protein product we call hemojuvelin. Analysis of Greek, Canadian and French families indicated that one mutation, the amino acid substitution G320V, was observed in all three populations and accounted for two-thirds of the mutations found. HFE2 transcript expression was restricted to liver, heart and skeletal muscle, similar to that of hepcidin, a key protein implicated in iron metabolism7,8,9. Urinary hepcidin levels were depressed in individuals with juvenile hemochromatosis, suggesting that hemojuvelin is probably not the hepcidin receptor. Rather, HFE2 seems to modulate hepcidin expression.

/pdf/mutations-in-hfe2-cause-iron-overload-in-chromosome-1q-a74d8plu2y.pdf

Owen Davidas

Papers

Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis.