Journal
BEHAVIOURAL BRAIN RESEARCH
Volume 296, Issue -, Pages 109-117Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbr.2015.09.003
Keywords
RRR-alpha-tocopherol quinine; Alzheimer's disease; Beta-amyloid oligomer; Neuroinflammation; NF-kappa B signaling; Oxidative stress
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Funding
- National Natural Science Foundation of China [81171014, 31471720, 31101335]
- National Science and Technology Major Projects of New Drugs [2012ZX09103301-001, 2014ZX09102045-006]
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The pathologies of Alzheimer's disease (AD) is associated with soluble beta-amyloid (A beta) oligomers, neuroinflammation and oxidative stress. Decreasing the levels of A beta oligomer, glial activation and oxidative stress are potential therapeutic approaches for AD treatment. We previously found alpha-tocopherol quinine (alpha-TQ) inhibited Ap aggregation and cytotoxicity, decreased the release of inflammatory cytokines and reactive oxygen species (ROS) in vitro. However, whether alpha-TQameliorates memory deficits and other neuropathologies in mice or patients with AD remains unknown. In this study, we reported that orally administered a-TQ ameliorated memory impairment in APPswe/PS1dE9 transgenic mice, decreased oxidative stress and the levels of A beta oligomer in the brains of mice, prevented the production of inducible nitric oxide synthase and inflammatory mediators, such as interleukin-6 and interleukin-1 beta, and inhibited microglial activation by inhibiting NF-kappa B signaling pathway. These findings suggest that alpha-TQ has potential therapeutic value for AD treatment. (C) 2015 Elsevier B.V. All rights reserved.
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