Nakaso Kazuhiro, Horikoshi Yosuke, Takahashi Toru, Hanaki Takehiko, Nakasone Masato, Kitagawa Yoshinori, Koike Taisuke, Matsura Tatsuya
Division of Medical Biochemistry, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, Japan.
Division of Medical Biochemistry, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, Japan.
Neurosci Lett. 2016 Jan 1;610:117-22. doi: 10.1016/j.neulet.2015.10.062. Epub 2015 Oct 30.
Neuroprotection following signal transduction has been investigated recently as a strategy for Parkinson's disease (PD) therapy. While oxidative stress is important in the pathogenesis of PD, neuroprotection using antioxidants such as α-tocopherol have not been successful. δ-tocotrienol (δT3), a member of the vitamin E family, has received attention because of activities other than its antioxidative effects. In the present study, we examined the estrogen receptor-β (ERβ)-mediated neuroprotective effects of δT3 in a mouse model of PD. ERβ is expressed in neuronal cells, including dopaminergic neurons in the substantia nigra. Daily forced oral administration of δT3 inhibited the loss of dopaminergic neurons in the substantia nigra. In addition, the ER inhibitor tamoxifen canceled the neuroprotective effects of δT3. Moreover, δT3 administration improved the performance of the PD mice in the wheel running activity, while tamoxifen inhibited this improved performance. These results suggest that the oral administration of δT3 may be useful in the treatment of PD patients, and ERβ may be a candidate target for the neuroprotection activity of δT3.
近年来，作为帕金森病（PD）治疗策略，对信号转导后的神经保护作用进行了研究。虽然氧化应激在PD发病机制中很重要，但使用抗氧化剂如α-生育酚进行神经保护尚未成功。δ-生育三烯酚（δT3）是维生素E家族的一员，因其除抗氧化作用外的其他活性而受到关注。在本研究中，我们在PD小鼠模型中研究了δT3通过雌激素受体-β（ERβ）介导的神经保护作用。ERβ在神经元细胞中表达，包括黑质中的多巴胺能神经元。每日强迫口服δT3可抑制黑质中多巴胺能神经元的丢失。此外，ER抑制剂他莫昔芬消除了δT3的神经保护作用。此外，给予δT3可改善PD小鼠在转轮活动中的表现，而他莫昔芬则抑制了这种改善的表现。这些结果表明，口服δT3可能对PD患者的治疗有用，并且ERβ可能是δT3神经保护活性的候选靶点。
