Nontoxic singlet oxygen generator as a therapeutic candidate for treating tauopathies.

Nontoxic singlet oxygen generator as a therapeutic candidate for treating tauopathies.
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DOI:
10.1038/srep10821
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发表时间:
2015-06-01
期刊:
影响因子:
4.6
通讯作者:
Yoshiike Y
Yoshiike Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sheik Mohideen S;Yamasaki Y;Omata Y;Tsuda L;Yoshiike Y

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亚甲蓝(MB)抑制tau的聚集,tau是神经元缠结的主要成分。然而,MB在体内的作用模式尚未完全了解。MB处理减少了表达人野生型tau的果蝇中肌氨酰不溶性tau的量。MB同时改善了攀登赤字的转基因tau苍蝇在有限的程度上,减少了野生型苍蝇的攀登活动。MB还降低了野生型果蝇的存活率。基于MB的光敏效应,我们推测在光下通过MB产生的单线态氧可能有助于MB在体内的有益和毒性作用。我们确定了虎红(RB)抑制tau积累和改善行为缺陷的程度低于MB。与MB不同,RB不会降低果蝇的存活率。我们的研究结果表明,毒性小的单线态氧发生剂可能是治疗tau蛋白病的合适候选药物。
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.
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