Effects of α-tocopherol on an animal model of tauopathies

Hanae Nakashima, Takeshi Ishihara, Osamu Yokota, Seishi Terada, John Q. Trojanowski, Virginia M Y Lee, Shigetoshi Kuroda

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73 Citations (Scopus)

Abstract

We have reported that transgenic (Tg) mice overexpressing human tau protein develop filamentous tau aggregates in the CNS. We overexpressed the smallest human tau isoform (T44) in the mouse CNS to model tauopathies. These tau Tg mice acquire age-dependent CNS pathologies, including insoluble, hyperphosphorylated tau and argyrophilic intraneuronal inclusions formed by tau-immunoreactive filaments. Therefore, these Tg mice are a model that can be exploited for drug discovery in studies that target amelioration of tau-induced neurodegeneration as well as for elucidating mechanisms of tau pathology in various neurodegenerative tauopathies. Oxidative stress has been implicated in the pathogenesis of various neurodegenerative diseases, including tauopathies, and many epidemiological, clinical, and basic studies have suggested the neuroprotective effects of vitamin E in neurodegenerative diseases. To elucidate the role of oxidative damage in the pathological mechanisms of these Tg mice, we fed them α-tocopherol, the major component of antioxidant vitamin E. Supplementation of α-tocopherol suppressed and/or delayed the development of tau pathology, which correlated with improvement in the health and attenuation of motor weakness in the Tg mice. These results suggest that oxidative damage is involved in the pathological mechanisms of the tau Tg mice and that treatment with antioxidative agents like α-tocopherol may prevent neurodegenerative tauopathies.

Original languageEnglish
Pages (from-to)176-186
Number of pages11
JournalFree Radical Biology and Medicine
Volume37
Issue number2
DOIs
Publication statusPublished - Jul 15 2004

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Keywords

  • α-Tocopherol
  • AD
  • Alzheimer's disease
  • Antioxidant
  • central nervous system
  • CNS
  • FA
  • formic acid
  • Free radicals
  • frontotemporal dementia with parkinsonism linked to chromosome 17
  • FTDP-17
  • MAb
  • Oxidative stress
  • Tauopathies
  • Transgenic mouse
  • Vitamin E

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Nakashima, H., Ishihara, T., Yokota, O., Terada, S., Trojanowski, J. Q., Lee, V. M. Y., & Kuroda, S. (2004). Effects of α-tocopherol on an animal model of tauopathies. Free Radical Biology and Medicine, 37(2), 176-186. https://doi.org/10.1016/j.freeradbiomed.2004.04.037