Cited by 298Heme Oxygenase-1 and Carbon MonoxideNeuroinflammation and Neurodegeneration MechanismsPorphyrin Metabolism and Disorders

Heme oxygenase-1 and neurodegeneration: expanding frontiers of engagement

Open access
Schipper, Hyman M., Song, Wei, Zukor, Hillel, Hascalovici, Jacob R., Zeligman, David·2009·Journal of Neurochemistry

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1111/j.1471-4159.2009.06160.x

Cites

184 of 184 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Up-regulation of HO-1 in glia might contribute to neurodegeneration; as brains age, prolonged action of HO-1 in astrocytes is likely to be involved in iron sequestration, intracellular oxidative stress, and mitochondrial insufficiency.

    “Although haem oxygenase 1 (HO-1) is considered to be cytoprotective, up-regulation of this enzyme in glia might contribute to neurodegeneration: as brains age, the prolonged action of HO-1 in astrocytes is likely to be involved in iron sequestration, intracellular oxidative stress, and mitochondrial insufficiency.56”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 7

  1. No claim to original US government works Journal Compilation Ó 2009 International Society for Neurochemistry, J. Neurochem. (2009) 110, 469-485 482
  2. H. M. Schipper et al. 14714159, 2009, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2009.06160.x, Wiley Online Library on [02/01/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
  3. Mann D. H. A. (1994) Vulnerability of specific neurons to aging, in Neurodegenerative Diseases (Calne D. B., ed.), pp. 15-31.
  4. Reichmann H. and Riederer P. (1994) Mitochondrial Disturbances in Neurodegeneration: Neurodegenerative Diseases. Saunders, Phila- delphia, PA.
  5. Schipper H. M. (1998b) Glial Iron Sequestration and Neurodegeneration, in Astrocytes in Brain Aging and Neurodegeneration (Schipper H. M., ed.), pp. 235-251.
  6. Schipper H. M. (2001) Mitochondrial iron deposition in aging astro- glia: mechanisms and disease implications, in Mitochondrial Ubiquinone (Coenzyme Q): Biochemical, Functional, Medical, and Therapeutic Aspects in Human Health and Disease (Ebadi M. and Chopra R. K., eds), pp. 267-280. Prominent Press, Scottsdale, AZ.
  7. Song W., Patel A., Qureshi H. Y., Han D., Schipper H. M. and Paudel H. K. (2009) The Parkinson disease-specific A30P mutation sta- bilizes alpha-synuclein against proteosomal degradation triggered by heme oxygenase 1 overexpression in human neuroblastoma cells. J. Neurochem., in press.

Cited by

Sorted by citations

Authors
Schipper, H. M., Song, W., Zukor, H., Hascalovici, J. R., & Zeligman, D.
Affiliations
Jewish General Hospital (CA)
Corresponding author
Schipper, Hyman M.
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2009-06-25
Volume
110
Issue
2
Pages
469-485
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
OpenAlex
W2001357290
Cited by
298
References
184
Citations by year
2026: 9 · 2025: 16 · 2024: 21 · 2023: 13 · 2022: 18 · 2021: 26 · 2020: 19 · 2019: 16 · 2018: 13 · 2017: 11 · 2016: 15 · 2015: 24 · 2014: 21 · 2013: 23 · 2012: 19
FWCI
1.35
Type
journal article
Language
en
Open access
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
Canadian Institutes of Health Research
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
Keywords
heme oxygenase-1, heme oxygenase-2, neurodegeneration, Alzheimer's disease, Parkinson's disease, mild cognitive impairment, astrocytes, Lewy bodies, amyloid plaques, neurofibrillary tangles, cerebral infarction, multiple sclerosis, iron metabolism, bilirubin, carbon monoxide, macroautophagy, neuroplasticity, protein aggregation
MeSH terms
Animals, Humans, Nerve Degeneration, Signal Transduction, Neurodegenerative Diseases, Heme Oxygenase-1

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review