α-Tocotrienol quinone modulates oxidative stress response and the biochemistry of aging

William D. Shrader, Akiko Amagata, Adam Barnes, Gregory M. Enns, Andrew Hinman, Orion Jankowski, Viktoria Kheifets, Ryo Komatsuzaki, Edgar Lee, Paul Mollard, Katsuyuki Murase, Alfredo A. Sadun, Martin Thoolen, Kieron Wesson, Guy Miller, William D. Shrader, Akiko Amagata, Adam Barnes, Gregory M. Enns, Andrew Hinman, Orion Jankowski, Viktoria Kheifets, Ryo Komatsuzaki, Edgar Lee, Paul Mollard, Katsuyuki Murase, Alfredo A. Sadun, Martin Thoolen, Kieron Wesson, Guy Miller

Index: Bioorg. Med. Chem. Lett. 21 , 3693-3698, (2011)

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Abstract

We report that α-tocotrienol quinone (ATQ3) is a metabolite of α-tocotrienol, and that ATQ3 is a potent cellular protectant against oxidative stress and aging. ATQ3 is orally bioavailable, crosses the blood-brain barrier, and has demonstrated clinical response in inherited mitochondrial disease in open label studies. ATQ3 activity is dependent upon reversible 2e-redox-cycling. ATQ3 may represent a broader class of unappreciated dietary-derived phytomolecular redox motifs that digitally encode biochemical data using redox state as a means to sense and transfer information essential for cellular function.Copyright © 2011 Elsevier Ltd. All rights reserved.