ミタニ シヨウヘイ   MITANI Shohei
  三谷 昌平
   所属   医学部 医学科
   職種   教授・講座主任
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Curcumin improves tau-induced neuronal dysfunction of nematodes.
掲載誌名 正式名:Neurobiology of aging
略  称:Neurobiol Aging
ISSNコード:(1558-1497)0197-4580(Linking)
掲載区分国外
巻・号・頁 39,69-81頁
著者・共著者 Miyasaka Tomohiro, Xie Ce, Yoshimura Satomi, Shinzaki Yuki, Yoshina Sawako, Kage-Nakadai Eriko, Mitani Shohei, Ihara Yasuo
発行年月 2016/03
概要 Tau is a key protein in the pathogenesis of various neurodegenerative diseases, which are categorized as tauopathies. Because the extent of tau pathologies is closely linked to that of neuronal loss and the clinical symptoms in Alzheimer's disease, anti-tau therapeutics, if any, could be beneficial to a broad spectrum of tauopathies. To learn more about tauopathy, we developed a novel transgenic nematode (Caenorhabditis elegans) model that expresses either wild-type or R406W tau in all the neurons. The wild-type tau-expressing worms exhibited uncoordinated movement (Unc) and neuritic abnormalities. Tau accumulated in abnormal neurites that lost microtubules. Similar abnormalities were found in the worms that expressed low levels of R406W-tau but were not in those expressing comparative levels of wild-type tau. Biochemical studies revealed that tau is aberrantly phosphorylated but forms no detergent-insoluble aggregates. Drug screening performed in these worms identified curcumin, a major phytochemical compound in turmeric, as a compound that reduces not only Unc but also the neuritic abnormalities in both wild-type and R406W tau-expressing worms. Our observations suggest that microtubule stabilization mediates the antitoxicity effect of curcumin. Curcumin is also effective in the worms expressing tau fragment, although it does not prevent the formation of tau-fragment dimers. These data indicate that curcumin improves the tau-induced neuronal dysfunction that is independent of insoluble aggregates of tau.
DOI 10.1016/j.neurobiolaging.2015.11.004
PMID 26923403