Journal
JOURNAL OF NEURAL TRANSMISSION
Volume 118, Issue 3, Pages 381-387Publisher
SPRINGER WIEN
DOI: 10.1007/s00702-010-0436-1
Keywords
Alzheimer disease; Heme oxygenase-1; Iron; Mild cognitive impairment; Mitochondria; Oxidative stress
Categories
Funding
- Canadian Institutes of Health Research
- Fonds de la Recherche en Sante du Quebec
- Alzheimer's Association (US)
- Institute for the Study of Aging
- Osta Biotechnologies Inc.
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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 beta-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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