title: Nontoxic singlet oxygen generator as a therapeutic candidate for treating tauopathies.
abstract: Methylene blue (MB) inhibits the aggregation of tau, a main constituent of neurofibrillary tangles. However, MB's mode of action in vivo is not fully understood. MB treatment reduced the amount of sarkosyl-insoluble tau in Drosophila that express human wild-type tau. MB concurrently ameliorated the climbing deficits of transgenic tau flies to a limited extent and diminished the climbing activity of wild-type flies. MB also decreased the survival rate of wild-type flies. Based on its photosensitive efficacies, we surmised that singlet oxygen generated through MB under light might contribute to both the beneficial and toxic effects of MB in vivo. We identified rose bengal (RB) that suppressed tau accumulation and ameliorated the behavioral deficits to a lesser extent than MB. Unlike MB, RB did not reduce the survival rate of flies. Our findings indicate that singlet oxygen generators with little toxicity may be suitable drug candidates for treating tauopathies.
authors.affiliation: Alzheimer's Disease Project Team, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, 7-430 Morioka, Obu, Aichi, Japan 474-8511.
authors.forename: Sahabudeen
authors.initials: S
authors.lastname: Sheik Mohideen
authors.affiliation: Department of Drug Discovery, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, 7-430 Morioka, Obu, Aichi, Japan 474-8511.
authors.forename: Yasutoyo
authors.initials: Y
authors.lastname: Yamasaki
authors.affiliation: Department of Occupational and Environmental Health, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan 466-8550.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Omata
authors.affiliation: Animal Models of Aging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, 7-430 Morioka, Obu, Aichi, Japan 474-8511.
authors.forename: Leo
authors.initials: L
authors.lastname: Tsuda
authors.affiliation: Alzheimer's Disease Project Team, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, 7-430 Morioka, Obu, Aichi, Japan 474-8511.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yoshiike
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001343:Autophagy; D001522:Behavior, Animal; D004195:Disease Models, Animal; D004330:Drosophila; D005260:Female; D006801:Humans; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D018384:Oxidative Stress; D026082:Singlet Oxygen / Q000378:metabolism*; D012995:Solubility; D024801:Tauopathies / Q000188:drug therapy / Q000378:metabolism*; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016875:tau Proteins; D026082:Singlet Oxygen; D008751:Methylene Blue