Abnormal localization of iron regulatory protein in Alzheimer’s disease
Abstract
A role for altered iron metabolism in the pathogenesis of Alzheimer's disease has been suggested by several reports associating the cardinal neuropathologic lesions with markers of free radical-induced damage and redox-active iron. We hypothesized that the abnormal distribution of iron in Alzheimer brain might result from alterations in iron regulatory proteins (IRP) such as IRP-1 and IRP-2, the main control elements of cellular iron homeostasis. Here, we report that while IRP-1 is present at similar levels in both Alzheimer and control brain tissue, IRP-2 shows striking differences and is associated with intraneuronal lesions, including neurofibrillary tangles, senile plaque neurites and neuropil threads. Since IRP-2 colocalizes with redox-active iron, our results suggest that alterations in IRP-2 might be directly linked to impaired iron homeostasis in Alzheimer's disease.
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Increased accumulation of iron in specific brain areas seems to be implicated in the neuropathology of various neurodegenerative disorders such as PD and AD.
“Increased accumulation of iron in specific brain areas seems to be implicated in the neuropathology of various neurodegenerative disorders such as PD and AD [50,51,52,53].”
From Beneficial Effects of Spirulina Consumption on Brain Health (2022) · cites this paper as [53]
Nuclear ferritin is glycosylated, with three potential glycosylation sites in the N-terminal region (Thr1, Thr2, Ser4) of ferritin H, whereas ferritin L contains only one (Ser2).
“Nuclear ferritin was found to be glycosylated, and three potential glycosylation sites were identified in the N-terminal region (Thr1, Thr2, and Ser4) of ferritin H, whereas the ferritin L subunit appeared to contain only one (Ser2) (285).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [285]
The glycosylation inhibitor alloxan prevented translocation of ferritin into the nucleus.
“the glycosylation inhibitor, alloxan, prevented translocation of ferritin into the nucleus”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [285]
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References 39 · Cited by 162
- Authors
- Smith, M. A., Wehr, K., Harris, P. L. R., Siedlak, S. L., Connor, J. R., & Perry, G.
- Affiliations
- Case Western Reserve University (US)
- European Molecular Biology Laboratory (DE)
- Pennsylvania State University (US)
- Corresponding author
- Smith, Mark A.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 1998-03
- Volume
- 788
- Issue
- 1-2
- Pages
- 232-236
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2077880605
- Cited by
- 162
- References
- 39
- Citations by year
- 2024: 1 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 1 · 2015: 1 · 2014: 3 · 2013: 6 · 2012: 6
- FWCI
- 7.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- Alzheimer's disease, IRP2, iron homeostasis, iron metabolism, redox-active iron, neurofibrillary tangles, amyloid plaques, neuropil threads, protein localization
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Energy Metabolism, Homeostasis, Humans, Immunohistochemistry, Iron-Sulfur Proteins, Middle Aged, Nerve Tissue Proteins, Oxidation-Reduction, Case-Control Studies, RNA-Binding Proteins, Oxidative Stress, Iron-Regulatory Proteins, Iron Regulatory Protein 1, Iron Regulatory Protein 2
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