Iron (III) induces aggregation of hyperphosphorylated tau and its reduction to iron (II) reverses the aggregation: implications in the formation of neurofibrillary tangles of Alzheimer's disease
- PMID:12358761
- DOI: 10.1046/j.1471-4159.2002.t01-1-01061.x
Iron (III) induces aggregation of hyperphosphorylated tau and its reduction to iron (II) reverses the aggregation: implications in the formation of neurofibrillary tangles of Alzheimer's disease
Erratum in
- J Neurochem. 2003 Sep;86(6):1568
Abstract
Iron as well as aluminum is reported to accumulate in neurons with neurofibrillary tangles (NFTs) of Alzheimer's disease (AD) brain. Previously we demonstrated that aluminum (III) shows phosphate-dependent binding with hyperphosphorylated tau (PHFtau), the major constituent of NFTs, thereby inducing aggregation of PHFtau. Herein we report that iron (III) can also induce aggregation of soluble PHFtau. Importantly, for the aggregation of PHFtau to occur, iron in the oxidized state (III) is essential since iron in the reduced state (II) lacks such ability. Furthermore, iron (III)-induced aggregation is reversed by reducing iron (III) to iron (II). Thus the iron-participating aggregation is mediated not only by tau phosphorylation but also by the transition of iron between reduced (II) and oxidized (III) states. Further incubation of insoluble PHFtau aggregates isolated from AD brain with reducing agents produced liberation of solubilized PHFtau and iron (II), indicating that PHFtau in association with iron (III) constitutes the insoluble pool of PHFtau. These results indicate that iron might play a role in the aggregation of PHFtau leading to the formation of NFTs in AD brain.
Similar articles
- A novel trivalent cation chelator Feralex dissociates binding of aluminum and iron associated with hyperphosphorylated tau of Alzheimer's disease.Shin RW, Kruck TP, Murayama H, Kitamoto T.Shin RW, et al.Brain Res. 2003 Jan 24;961(1):139-46. doi: 10.1016/s0006-8993(02)03893-3.Brain Res. 2003.PMID:12535786
- Neurofibrillary tangles in progressive supranuclear palsy contain the same tau epitopes identified in Alzheimer's disease PHFtau.Schmidt ML, Huang R, Martin JA, Henley J, Mawal-Dewan M, Hurtig HI, Lee VM, Trojanowski JQ.Schmidt ML, et al.J Neuropathol Exp Neurol. 1996 May;55(5):534-9. doi: 10.1097/00005072-199605000-00006.J Neuropathol Exp Neurol. 1996.PMID:8627344
- Identification of phosphorylation sites in PHF-TAU from patients with Guam amyotrophic lateral sclerosis/parkinsonism-dementia complex.Mawal-Dewan M, Schmidt ML, Balin B, Perl DP, Lee VM, Trojanowski JQ.Mawal-Dewan M, et al.J Neuropathol Exp Neurol. 1996 Oct;55(10):1051-9.J Neuropathol Exp Neurol. 1996.PMID:8858002
- Phosphorylation of paired helical filament tau in Alzheimer's disease neurofibrillary lesions: focusing on phosphatases.Trojanowski JQ, Lee VM.Trojanowski JQ, et al.FASEB J. 1995 Dec;9(15):1570-6. doi: 10.1096/fasebj.9.15.8529836.FASEB J. 1995.PMID:8529836Review.
- Interaction of aluminum with paired helical filament tau is involved in neurofibrillary pathology of Alzheimer's disease.Shin RW.Shin RW.Gerontology. 1997;43 Suppl 1:16-23. doi: 10.1159/000213882.Gerontology. 1997.PMID:9187935Review.
Cited by
- Revisiting the intersection of amyloid, pathologically modified tau and iron in Alzheimer's disease from a ferroptosis perspective.Derry PJ, Hegde ML, Jackson GR, Kayed R, Tour JM, Tsai AL, Kent TA.Derry PJ, et al.Prog Neurobiol. 2020 Jan;184:101716. doi: 10.1016/j.pneurobio.2019.101716. Epub 2019 Oct 8.Prog Neurobiol. 2020.PMID:31604111Free PMC article.Review.
- Effects of Deferasirox in Alzheimer's Disease and Tauopathy Animal Models.Kwan P, Ho A, Baum L.Kwan P, et al.Biomolecules. 2022 Feb 25;12(3):365. doi: 10.3390/biom12030365.Biomolecules. 2022.PMID:35327557Free PMC article.
- Parkinson's Disease Dementia: Synergistic Effects of Alpha-Synuclein, Tau, Beta-Amyloid, and Iron.Han J, Fan Y, Wu P, Huang Z, Li X, Zhao L, Ji Y, Zhu M.Han J, et al.Front Aging Neurosci. 2021 Oct 11;13:743754. doi: 10.3389/fnagi.2021.743754. eCollection 2021.Front Aging Neurosci. 2021.PMID:34707492Free PMC article.
- Metal Ion Effects on Aβ and Tau Aggregation.Kim AC, Lim S, Kim YK.Kim AC, et al.Int J Mol Sci. 2018 Jan 2;19(1):128. doi: 10.3390/ijms19010128.Int J Mol Sci. 2018.PMID:29301328Free PMC article.Review.
- Dysregulation of Neuronal Iron in Alzheimer's Disease.Uddin MS, Ashraf GM.Uddin MS, et al.Curr Neuropharmacol. 2023;21(11):2247-2250. doi: 10.2174/1570159X20666211231163544.Curr Neuropharmacol. 2023.PMID:34970955Free PMC article.No abstract available.
Publication types
MeSH terms
Substances
Related information
LinkOut - more resources
Full Text Sources
Medical