Heme oxygenase-1 and neurodegeneration: Expanding frontiers of engagement

Hyman M. Schipper, Wei Song, Hillel Zukor, Jacob R. Hascalovici, David Zeligman

Research output: Contribution to journalReview article

162 Citations (Scopus)

Abstract

The heme oxygenases (HOs), responsible for the degradation of heme to biliverdin/bilirubin, free iron and CO, have been heavily implicated in mammalian CNS aging and disease. In normal brain, the expression of HO-2 is constitutive, abundant and fairly ubiquitous, whereas HO-1 mRNA and protein are confined to small populations of scattered neurons and neuroglia. In contradistinction to HO-2, the ho-1 gene (Hmox1) is exquisitely sensitive to induction by a wide range of pro-oxidant and other stressors. In Alzheimer disease and mild cognitive impairment, immunoreactive HO-1 protein is over-expressed in neurons and astrocytes of the cerebral cortex and hippocampus relative to age-matched, cognitively intact controls and co-localizes to senile plaques, neurofibrillary tangles, and corpora amylacea. In Parkinson disease, HO-1 is markedly over-expressed in astrocytes of the substantia nigra and decorates Lewy bodies in affected dopaminergic neurons. HMOX1 is also up-regulated in glial cells surrounding human cerebral infarcts, hemorrhages and contusions, within multiple sclerosis plaques, and in other degenerative and inflammatory human CNS disorders. Heme-derived free ferrous iron, CO, and biliverdin/bilirubin are biologically active substances that have been shown to either ameliorate or exacerbate neural injury contingent upon specific disease models employed, the intensity and duration of HO-1 expression and the nature of the prevailing redox microenvironment. In 'stressed' astroglia, HO-1 hyperactivity promotes mitochondrial sequestration of non-transferrin iron and macroautophagy and may thereby contribute to the pathological iron deposition and bioenergetic failure amply documented in Alzheimer disease, Parkinson disease and other aging-related neurodegenerative disorders. Glial HO-1 expression may also impact cell survival and neuroplasticity in these conditions by modulating brain sterol metabolism and proteosomal degradation of neurotoxic protein aggregates.

Original languageEnglish (US)
Pages (from-to)469-485
Number of pages17
JournalJournal of Neurochemistry
Volume110
Issue number2
DOIs
StatePublished - Jul 1 2009
Externally publishedYes

Fingerprint

Heme Oxygenase-1
Iron
Neuroglia
Astrocytes
Biliverdine
Neurons
Carbon Monoxide
Heme
Bilirubin
Parkinson Disease
Brain
Alzheimer Disease
Aging of materials
Lewy Bodies
Heme Oxygenase (Decyclizing)
Degradation
Neurofibrillary Tangles
Neuronal Plasticity
Dopaminergic Neurons
Central Nervous System Diseases

Keywords

  • Aging
  • Alzheimer disease
  • Heme oxygenase-1
  • Iron
  • Oxidative stress
  • Parkinson disease

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Heme oxygenase-1 and neurodegeneration : Expanding frontiers of engagement. / Schipper, Hyman M.; Song, Wei; Zukor, Hillel; Hascalovici, Jacob R.; Zeligman, David.

In: Journal of Neurochemistry, Vol. 110, No. 2, 01.07.2009, p. 469-485.

Research output: Contribution to journalReview article

Schipper, Hyman M. ; Song, Wei ; Zukor, Hillel ; Hascalovici, Jacob R. ; Zeligman, David. / Heme oxygenase-1 and neurodegeneration : Expanding frontiers of engagement. In: Journal of Neurochemistry. 2009 ; Vol. 110, No. 2. pp. 469-485.
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