Methylene blue reduces aβ levels and rescues early cognitive deficit by increasing proteasome activity.
Methylene blue reduces aβ levels and rescues early cognitive deficit by increasing proteasome activity.
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DOI：
10.1111/j.1750-3639.2010.00430.x
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发表时间：
2011-03
期刊：
影响因子：
--
通讯作者：
Oddo S
中科院分区：
文献类型：
--
作者：
Medina DX;Caccamo A;Oddo S
一项测试亚甲基蓝（MB）作为阿尔茨海默病（AD）潜在治疗药物的II期临床试验取得了令人鼓舞的结果，据报道，经过6个月的MB治疗后，AD患者的认知功能有所改善。尽管有这些报道，但尚未发表MB在哺乳动物中的临床前试验，因此其与AD病理相关的作用机制仍然未知。为了阐明MB对AD病理的影响并确定其作用机制，我们使用了小鼠模型（3xTg-AD），该模型会产生年龄依赖性的a β和tau积累以及认知能力下降。在这里，我们报道慢性饮食MB治疗降低了3xTg-AD小鼠的Aβ水平并改善了学习和记忆缺陷。MB对Aβ病理影响的潜在机制似乎是通过Aβ清除率的增加介导的，因为我们发现MB增加了大脑中蛋白酶体的凝乳胰蛋白酶和胰蛋白酶样活性。据我们所知，这是第一个显示MB在体内增加蛋白酶体功能和改善ad样病理的报告。总的来说，本文提供的数据支持使用MB治疗AD，并提供了一种可能的作用机制。
Promising results have emerged from a phase II clinical trial testing Methylene blue (MB) as a potential therapeutic for Alzheimer disease (AD), where improvements in cognitive functions of AD patients after 6 months of MB administration have been reported. Despite these reports, no preclinical testing of MB in mammals has been published, and thus its mechanism of action in relation to AD pathology remains unknown. In order to elucidate the effects of MB on AD pathology and to determine its mechanism of action, we used a mouse model (3xTg-AD) that develops age-dependent accumulation of Aβ and tau and cognitive decline. Here, we report that chronic dietary MB treatment reduces Aβ levels and improves learning and memory deficits in the 3xTg-AD mice. The mechanisms underlying the effects of MB on Aβ pathology appears to be mediated by an increase in Aβ clearance as we show that MB increases the chymotrypsin-and trypsin-like activities of the proteasome in the brain. To our knowledge, this is the first report showing that MB increases proteasome function and ameliorates AD-like pathology in vivo. Overall, the data presented here support the use of MB for the treatment of AD and offer a possible mechanism of action.
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影响因子：
5.3
作者：
Oddo S
通讯作者：
Oddo S
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Lauterburg, BH
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