title: Curcumin improves tau-induced neuronal dysfunction of nematodes.
abstract: 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.
authors.affiliation: Faculty of Medical and Life Sciences, Department of Neuropathology, Doshisha University, Kyotanabe-shi, Kyoto, Japan. Electronic address: tomiyasa@mail.doshisha.ac.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Miyasaka
authors.affiliation: Faculty of Medical and Life Sciences, Department of Neuropathology, Doshisha University, Kyotanabe-shi, Kyoto, Japan.
authors.forename: Ce
authors.initials: C
authors.lastname: Xie
authors.affiliation: Faculty of Medical and Life Sciences, Department of Neuropathology, Doshisha University, Kyotanabe-shi, Kyoto, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Yoshimura
authors.affiliation: Faculty of Medical and Life Sciences, Department of Neuropathology, Doshisha University, Kyotanabe-shi, Kyoto, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Shinzaki
authors.affiliation: Department of Physiology, Tokyo Women's Medical University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Sawako
authors.initials: S
authors.lastname: Yoshina
authors.affiliation: Department of Physiology, Tokyo Women's Medical University School of Medicine, Shinjuku-ku, Tokyo, Japan; Advanced Research Institute for Natural Science and Technology, Osaka City University, Sumiyoshi-ku, Osaka, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Kage-Nakadai
authors.affiliation: Department of Physiology, Tokyo Women's Medical University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Mitani
authors.affiliation: Faculty of Medical and Life Sciences, Department of Neuropathology, Doshisha University, Kyotanabe-shi, Kyoto, Japan; Laboratory for Cognition and Aging, Graduate School of Brain Sciences, Doshisha University, Kizugawa-shi, Kyoto, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ihara
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000502:physiology*; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015870:Gene Expression; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D066263:Protein Aggregation, Pathological; D024801:Tauopathies / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins; D003474:Curcumin
keywords: Caenorhabditis elegans; Curcumin; Microtubules; Neurite; Neuronal dysfunction; Tau