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 language | English |
|---|---|
| Pages (from-to) | 886-892 |
| Number of pages | 7 |
| Journal | Neurochemistry International |
| Volume | 56 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 2010 Jul 1 |
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Keywords
- Alzheimer's disease
- Oxidative stress
- PHF
- Tau
- Tau-binding proteins
- Triose phosphate isomerase
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
- Cell Biology
Cite this
Effects of Tau on the activity of triose phosphate isomerase (TPI) in brain cells. / Park, Seung Ah; Park, Hye Won; Kim, Nam Hee; Kim, Yoon Ha; Kwak, Min Jeong; Shin, Jun Seop; Kim, Chan Wha.
In: Neurochemistry International, Vol. 56, No. 8, 01.07.2010, p. 886-892.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of Tau on the activity of triose phosphate isomerase (TPI) in brain cells
AU - Park, Seung Ah
AU - Park, Hye Won
AU - Kim, Nam Hee
AU - Kim, Yoon Ha
AU - Kwak, Min Jeong
AU - Shin, Jun Seop
AU - Kim, Chan Wha
PY - 2010/7/1
Y1 - 2010/7/1
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Oxidative stress
KW - PHF
KW - Tau
KW - Tau-binding proteins
KW - Triose phosphate isomerase
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U2 - 10.1016/j.neuint.2010.03.014
DO - 10.1016/j.neuint.2010.03.014
M3 - Article
VL - 56
SP - 886
EP - 892
JO - Neurochemistry International
JF - Neurochemistry International
SN - 0197-0186
IS - 8
ER -