Heme oxygenase-1 in Alzheimer disease: a tribute to Moussa Youdim.
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.
Schipper
Hyman M
HM
Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Cote St. Catherine Road, Montreal, QC, H3T 1E2, Canada. hyman.schipper@mcgill.ca
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003072:Cognition Disorders / Q000378:metabolism* / Q000473:pathology; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D049673:History, 20th Century; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology
D051547:Heme Oxygenase-1