Effects of Tau on the activity of triose phosphate isomerase (TPI) in brain cells.
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.
Park
Seung-Ah
SA
School of Life Sciences and Biotechnology, Korea University, 1, 5-ga Anam-dong, Sungbuk-ku, Seoul 136-701, Republic of Korea.
Park
Hye Won
HW
Kim
Nam-Hee
NH
Kim
Yoon-Ha
YH
Kwak
Min-Jeong
MJ
Shin
Jun-Seop
JS
Kim
Chan-Wha
CW
D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D019636:Neurodegenerative Diseases / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000201:enzymology / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics; D010766:Phosphorylation; D014305:Triose-Phosphate Isomerase / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics / Q000502:physiology*
D016875:tau Proteins; D014305:Triose-Phosphate Isomerase