Effects of Tau on the activity of triose phosphate isomerase (TPI) in brain cells

Seung Ah Park, Hye Won Park, Nam Hee Kim, Yoon Ha Kim, Min Jeong Kwak, Jun Seop Shin, Chan Wha Kim

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Tau is a main component of the aberrant paired helical filaments (PHF) found in Alzheimer's disease (AD). It has also been reported to enhance oxidative stress, which is a major factor in the pathogenesis of neurodegenerative diseases. However, protective functions of Tau have recently been reported, including antagonizing apoptosis, in addition to its role in stabilizing microtubules. In this study, the interaction between Tau and triose phosphate isomerase (TPI) in a normal, nondisease state as well as in a neurodegeneration state was examined and demonstrated for the first time. More importantly, we also showed that Tau protects TPI against oxidative damage. An oxidative stress-induced decrease in the activity of TPI was attenuated in Tau-overexpressing cells, indicating that Tau protects TPI against oxidative damage. By contrast, the activity of TPI was decreased in Tau-transgenic (Tg) mice compared to non-Tg (NTg) mice even though protein levels were not changed in both groups. Some TPIs were found on the PHF in Tg mice, which explains the decrease in the activity of TPI. Taken together, we concluded that while Tau binds and protects TPI in normal cells, and conversely, the formation of PHF induced by Tau phosphorylation trap some TPI and trigger the functional loss of TPI in the development of neurodegenerative diseases. Our results provide new insights into understanding the in-depth involvement of Tau in the development of neurodegenerative disorders.

Original languageEnglish
Pages (from-to)886-892
Number of pages7
JournalNeurochemistry International
Volume56
Issue number8
DOIs
Publication statusPublished - 2010 Jul

Keywords

  • Alzheimer's disease
  • Oxidative stress
  • PHF
  • Tau
  • Tau-binding proteins
  • Triose phosphate isomerase

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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