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Iron Deficiency and Overload pp 125–139Cite as

Brain Iron Deposition in Aging and Disease: Role of HO-1

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Summary

• Mechanisms responsible for the pathological deposition of redox-active iron in the aging and degenerating human brain remain incompletely understood.

• Heme oxygenase-1 (HO-1) is a 32-kDa stress protein that degrades heme to biliverdin, free iron, and carbon monoxide.

• Brain HO-1 expression increases with advancing age, and the enzyme is further induced in CNS tissues affected by Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative and neuroinflammatory conditions.

• Upregulation of HO-1 in astrocytes exacerbates intracellular oxidative stress and promotes sequestration of non-transferrin-derived iron by the mitochondrial compartment.

• The glial mitochondrial iron catalyzes the bio-activation of protoxins (e.g., catechols, MPTP) to potent neurotoxins (o-semiquinones, MPP+) and may further facilitate neural injury by attenuating glutathione biosynthesis and other ATP-dependent processes.

• Suppression of glial HO-1 induction or activity may constitute a rational therapeutic approach to curtail pathological iron deposition and mitochondrial insufficiency in disorders of the aging human CNS.

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Acknowledgments

The author thanks Adrienne Liberman for assistance with the preparation of this manuscript. Contributions by the Schipper laboratory were enabled by grants from the Canadian Institutes of Health Research, the Fonds de la Recherche en Santé du Québec, the Alzheimer’s Association (US), and the Parkinson Foundation of Canada.

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Authors and Affiliations

  1. Department Neurology &Neurosurgery, Lady Davis Institute for Medical Research, Centre for Neurotranslational Research, Sir Mortimer B. Davis- Jewish General Hospital, McGill University, Montreal, Quebec, Canada

    Hyman M. Schipper MD, PHD FRPC

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  1. Hyman M. Schipper MD, PHD FRPC
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Editors and Affiliations

  1. Dept. Psychology, Bar-Ilan University, Ramat Gan, 52900, Israel

    Shlomo Yehuda

  2. Dept. Psychology, Boston University, Cummington St. 64, Boston, 02215-2407, USA

    David I. Mostofsky

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Schipper, H.M. (2009). Brain Iron Deposition in Aging and Disease: Role of HO-1. In: Yehuda, S., Mostofsky, D. (eds) Iron Deficiency and Overload. Nutrition and Health. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59745-462-9_7

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