• Targeting Iron

    From ironjustice@21:1/5 to All on Thu Nov 29 11:53:00 2018
    Iron as a Therapeutic Target in HFE-Related Hemochromatosis: Usual and Novel Aspects
    Olivier Loréal * , Thibault Cavey, François Robin, Moussa Kenawi, Pascal Guggenbuhl and Pierre Brissot
    Pharmaceuticals 2018, 11(4), 131; https://doi.org/10.3390/ph11040131
    INSERM, Univ Rennes, INRA, CHU Rennes, Institut NUMECAN (Nutrition Metabolisms and Cancer), F-35033 Rennes, France
    Received: 28 August 2018 / Revised: 16 November 2018 / Accepted: 19 November 2018 / Published: 26 November 2018
    Special Issue Iron as Therapeutic Targets in Human Diseases)

    Genetic hemochromatosis is an iron overload disease that is mainly related to the C282Y mutation in the HFE gene. This gene controls the expression of hepcidin, a peptide secreted in plasma by the liver and regulates systemic iron distribution.
    Homozygous C282Y mutation induces hepcidin deficiency, leading to increased circulating transferrin saturation, and ultimately, iron accumulation in organs such as the liver, pancreas, heart, and bone. Iron in excess may induce or favor the development
    of complications such as cirrhosis, liver cancer, diabetes, heart failure, hypogonadism, but also complaints such as asthenia and disabling arthritis. Iron depletive treatment mainly consists of venesections that permit the removal of iron contained in
    red blood cells and the subsequent mobilization of stored iron in order to synthesize hemoglobin for new erythrocytes. It is highly efficient in removing excess iron and preventing most of the complications associated with excess iron in the body.
    However, this treatment does not target the biological mechanisms involved in the iron metabolism disturbance. New treatments based on the increase of hepcidin levels, by using hepcidin mimetics or inducers, or inhibitors of the iron export activity of
    ferroportin protein that is the target of hepcidin, if devoid of significant secondary effects, should be useful to better control iron parameters and symptoms, such as arthritis.

    Full-Text https://www.mdpi.com/1424-8247/11/4/131/htm

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