Methylene blue and dimebon inhibit aggregation of TDP-43 in cellular models
Methylene blue and dimebon inhibit aggregation of TDP-43 in cellular models
复制标题
DOI：
10.1016/j.febslet.2009.06.042
复制
发表时间：
2009-07-21
期刊：
影响因子：
3.5
通讯作者：
Hasegawa, Masato
中科院分区：
文献类型：
--
作者：
Yamashita, Makiko;Nonaka, Takashi;Hasegawa, Masato
肌萎缩侧索硬化症（ALS）和额颞叶变性伴泛素化包涵体（FTLD-U）是TDP-43病理学的主要神经退行性疾病。在这里，我们研究了亚甲基蓝（MB）和dimebon，两种化合物，已被报道是有益的阿尔茨海默病（AD）的II期临床试验中，在SH-SY 5 Y细胞中TDP-43聚集体的形成的影响。用0.05 μ M MB或5 μ M dimebon处理后，TDP-43聚集体的数量分别减少了50%和45%。甲基溴和二甲苯醚的联合使用使这一数量减少了80%。免疫印迹分析证实了这些发现。结果表明，MB和Dimebon可用于治疗ALS、FTLD-U和其他TDP-43蛋白病。(C)2009年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) are major neurodegenerative diseases with TDP-43 pathology. Here we investigated the effects of methylene blue (MB) and dimebon, two compounds that have been reported to be beneficial in phase II clinical trials of Alzheimer's disease (AD), on the formation of TDP-43 aggregates in SH-SY5Y cells. Following treatment with 0.05 mu M MB or 5 mu M dimebon, the number of TDP-43 aggregates was reduced by 50% and 45%, respectively. The combined use of MB and dimebon resulted in a 80% reduction in the number. These findings were confirmed by immunoblot analysis. The results indicate that MB and dimebon may be useful for the treatment of ALS, FTLD-U and other TDP-43 proteinopathies. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.