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Heme oxygenase-1 in Alzheimer disease: a tribute to Moussa Youdim

  • Basic Neurosciences, Genetics and Immunology - Review Article
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Abstract

Heme oxygenase-1 (HO-1), a 32 kDa stress protein mediating the degradation of heme to ferrous iron, carbon monoxide and biliverdin/bilirubin, has been implicated in the pathogenesis of Alzheimer disease (AD) and other aging-related neurodegenerative disorders. In AD and mild cognitive impairment (MCI), immunoreactive HO-1 protein is over-expressed in astrocytes and neurons of the hippocampus and cerebral cortex and co-localizes to neurofibrillary tangles, senile plaques and corpora amylacea. Astroglial induction of the Hmox1 gene by β-amyloid, pro-inflammatory cytokines and hydrogen peroxide promotes mitochondrial sequestration of non-transferrin iron and macroautophagy and may thereby contribute to the pathological iron deposition and bioenergy failure amply documented in AD-affected neural tissues. Glial HO-1 expression may also impact cell survival and neuroplasticity in AD by modulating brain sterol/oxysterol metabolism and the degradation of tau by the proteasome. Suppression of glial HO-1 activity by pharmacological or other means may confer neuroprotection in AD by curtailing iron-mediated neurotoxicity.

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Acknowledgments

Contributions from the host laboratory reported herein were supported by grants from the Canadian Institutes of Health Research, the Fonds de la Recherche en Santé du Québec, the Alzheimer’s Association (US), the Institute for the Study of Aging, and Osta Biotechnologies Inc.

Conflict of interest statement

The author has served as consultant to Osta Biotechnologies, Molecular Biometrics Inc., TEVA Neurosciences and Caprion Pharmaceuticals. He holds stock options in Osta and equity in Molecular Biometrics Inc.

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  1. Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Cote St. Catherine Road, Montreal, QC, H3T 1E2, Canada

    Hyman M. Schipper

  2. Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada

    Hyman M. Schipper

  3. Department of Medicine (Geriatrics), McGill University, Montreal, QC, Canada

    Hyman M. Schipper

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Correspondence to Hyman M. Schipper.

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Schipper, H.M. Heme oxygenase-1 in Alzheimer disease: a tribute to Moussa Youdim. J Neural Transm 118, 381–387 (2011). https://doi.org/10.1007/s00702-010-0436-1

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