Iron Deposition Leads to Hyperphosphorylation of Tau and Disruption of Insulin Signaling
Open accessAbstract
Iron deposition in the brain is an early issue in Alzheimer’s disease (AD). However, the pathogenesis of iron-induced pathological changes in AD remains elusive. Insulin resistance in brains is an essential feature of AD. Previous studies determined that insulin resistance is involved in the development of pathologies in AD. Tau pathology is one of most important hallmarks in AD and is associated with the impairment of cognition and clinical grades of the disease. In the present study, we observed that ferrous (Fe2+) chloride led to aberrant phosphorylation of tau, and decreased tyrosine phosphorylation levels of insulin receptor β (IRβ), insulin signal substrate 1 (IRS-1) and phosphoinositide 3-kinase p85α (PI3K p85α), in primary cultured neurons. In the in vivo studies using mice with supplemented dietary iron, learning and memory was impaired. As well, hyperphosphorylation of tau and disrupted insulin signaling in the brain was induced in iron-overloaded mice. Furthermore, in our in vitro work we identified the activation of insulin signaling following exogenous supplementation of insulin. This was further attenuated by iron-induced hyperphosphorylation of tau in primary neurons. Together, these data suggest that dysfunctional insulin signaling participates in iron-induced abnormal phosphorylation of tau in AD. Our study highlights the promising role of insulin signaling in pathological lesions induced by iron overloading.
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Iron is involved in hyperphosphorylation of tau protein through dysfunctional insulin signalling.
“iron is involved in the hyperphosphorylation of tau protein through dysfunctional insulin signalling.”
From Role of Tau Protein in Neurodegenerative Diseases and Development of Its Targeted Drugs: A Literature Review (2024) · cites this paper as [146]
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“The hyperphosphorylation of tau and disruption of insulin signalling in the brain were reported to be induced in iron-overloaded mice [146].”
Background
- Authors
- Wan, W., Cao, L., Kalionis, B., Murthi, P., Xia, S., & Guan, Y.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Shanghai Medical College of Fudan University (CN)
- Royal Women's Hospital (AU)
- The University of Melbourne (AU)
- Fudan University (CN)
- Corresponding author
- Xia, Shijin
- Guan, Yangtai
- Venue
- Frontiers in Neurology
- Publisher
- Frontiers Media SA
- Published
- 2019-06-19
- Volume
- 10
- Pages
- 607-607
- ISSN
- 1664-2295 (ISSN-L)
- PMC
- PMC6593079
- OpenAlex
- W2952790855
- Cited by
- 84
- References
- 90
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 20 · 2023: 12 · 2022: 14 · 2021: 6 · 2020: 6 · 2019: 2
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Neurology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81230027, 81771295, 81801043)
- Shanghai Municipal Education Commission (TM201508, YS2017ZY050083)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- iron accumulation, tau hyperphosphorylation, insulin signaling, insulin resistance, Alzheimer's disease, iron overload, dietary iron supplementation, insulin receptor beta, IRS-1, PI3K p85α, learning and memory impairment, primary neurons
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 ›
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