Long-term overexpression of heme oxygenase 1 promotes tau aggregation in mouse brain by inducing tau phosphorylation
Open accessAbstract
Intracellular tau aggregates composed of neurofibrillary tangles (NFTs) are a defining feature of Alzheimer's disease (AD). Increased expression of heme oxygenase-1 (HO-1) is a common phenomenon in AD. Interestingly, the spatial distribution of HO-1 expression is essentially identical to that of pathological accumulation of tau in AD. In this study, we developed a new transgenic mouse overexpressing HO-1, called CAG-HO-1 Tg mice, to explore the relationship between HO-1 and tau aggregation. In this model, we found that long-term overexpression of HO-1 significantly promoted tau aggregation in brain, by analyzing changes in morphology and insoluble tau expression levels. Moreover, our research provides the first in vivo evidence that HO-1 can enhance iron loading and tau (Ser199/202/396) phosphorylation in brains of transgenic mice. Cellular evidence indicates that HO-1 can induce the phosphorylation of tau through iron accumulation in Neuro2a cells stably transfected with HO-1. Our data suggest that long-term overexpression of HO-1 can promote tau aggregation. This mechanism involves excessive iron production mediated by HO-1 overexpression, which induces tau phosphorylation. Our results provide a potential pathway for the pathogenesis of tauopathies, which remains largely unknown.
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Overexpression of HO-1 in mice leads to iron loading and tau aggregation in the brain, which are characteristic of Alzheimer's disease.
“Overexpression of HO-1 in mice leads to iron loading and tau aggregation in the brain, which are characteristic of Alzheimer’s disease.97”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [97]
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The role of iron in brain ageing and neurodegenerative disorders
Ward, R. J., Zucca, F. A., Duyn, J. H., Crichton, R. R., & Zecca, L. (2014) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70117-6 · Cited by 1,819 · see citing works
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Iron Pathophysiology in Alzheimer’s Diseases
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- Authors
- Hui, Y., Wang, D., Li, W., Zhang, L., Jin, J., Ma, N., Zhou, L., Nakajima, O., Zhao, W., & Gao, X.
- Affiliations
- Harbin Medical University (CN)
- Yamagata University (JP)
- Venue
- Journal of Alzheimer s Disease
- Publisher
- SAGE Publications
- Published
- 2011-09-09
- Volume
- 26
- Issue
- 2
- Pages
- 299-313
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1825967587
- Cited by
- 71
- References
- 54
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 8 · 2023: 4 · 2022: 4 · 2021: 1 · 2020: 5 · 2019: 3 · 2018: 5 · 2017: 5 · 2016: 4 · 2015: 4 · 2014: 7 · 2013: 6 · 2012: 4
- FWCI
- 3.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Alzheimer s Disease (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (30971059)
- Natural Science Foundation of Heilongjiang Province
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- heme oxygenase-1, tau aggregation
- MeSH terms
- Alzheimer Disease, Animals, Brain, Disease Models, Animal, Mice, Transgenic, Neurons, Phosphorylation, Neurofibrillary Tangles, tau Proteins, Mice, Heme Oxygenase-1
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