Iron (III) induces aggregation of hyperphosphorylated τ and its reduction to iron (II) reverses the aggregation: implications in the formation of neurofibrillary tangles of Alzheimer's disease
Article first published online: 3 FEB 2004
Journal of Neurochemistry
Volume 82, Issue 5, pages 1137–1147, September 2002
How to Cite
Yamamoto, A., Shin, R.-W., Hasegawa, K., Naiki, H., Sato, H., Yoshimasu, F. and Kitamoto, T. (2002), Iron (III) induces aggregation of hyperphosphorylated τ and its reduction to iron (II) reverses the aggregation: implications in the formation of neurofibrillary tangles of Alzheimer's disease. Journal of Neurochemistry, 82: 1137–1147. doi: 10.1046/j.1471-4159.2002.t01-1-01061.x
- Issue published online: 3 FEB 2004
- Article first published online: 3 FEB 2004
- Received May 9, 2002; accepted May 15, 2002.
- Alzheimer's disease;
- protein aggregation;
- τ protein
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 τ (PHFτ), the major constituent of NFTs, thereby inducing aggregation of PHFτ. Herein we report that iron (III) can also induce aggregation of soluble PHFτ. Importantly, for the aggregation of PHFτ 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 τ phosphorylation but also by the transition of iron between reduced (II) and oxidized (III) states. Further incubation of insoluble PHFτ aggregates isolated from AD brain with reducing agents produced liberation of solubilized PHFτ and iron (II), indicating that PHFτ in association with iron (III) constitutes the insoluble pool of PHFτ. These results indicate that iron might play a role in the aggregation of PHFτ leading to the formation of NFTs in AD brain.