Novel therapeutic strategies for neurodegenerative disease.
Novel therapeutic strategies for neurodegenerative disease.
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DOI：
10.1111/j.1479-8301.2009.00289.x
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发表时间：
2009-06
期刊：
影响因子：
--
通讯作者：
Takeda M
中科院分区：
文献类型：
--
作者：
Tanimukai H;Kudo T;Tanaka T;Grundke-Iqbal I;Iqbal K;Takeda M
蛋白磷酸酶2A（PP 2A）的活性受损，被认为是阿尔茨海默病（AD）脑中tau异常过度磷酸化的原因。PP 2A的活性受两种内源性抑制蛋白I1 PP 2A和I2 PP 2A的调节。此前，我们曾报道：（i）I1 PP 2A和I2 PP 2A在AD脑中的神经元细胞中随着I2 PP 2A全蛋白的切割和其氨基末端片段从细胞核易位到细胞质而上调;和（ii）易位的I2 PP 2A不仅与PP 2A催化亚基共定位，而且与神经元细胞质中的磷酸化tau共定位。此外，根据初步数据，I2 PP 2A的切割位点位于I2 PP 2A序列的氨基酸175和176之间。由于I2 PP 2A上的氨基酸168至181的序列可能作为核定位信号（NLS）起作用，因此抑制I2 PP 2A中NLS的分解有望成为治疗阿尔茨海默病的新的治疗靶点。
The activity of protein phosphatase 2A (PP2A) is compromised and believed to be the cause of the abnormal hyperphosphorylation of tau in Alzheimer’s disease (AD) brain. Activity of PP2A is regulated by two endogeneous inhibitor proteins, called as I1PP2A and I2PP2A. Previously, we reported that: (i) I1PP2A and I2PP2A are upregulated with cleavage of I2PP2A holoprotein and translocation of its amino terminal fragment from the nucleus to the cytoplasm in neuronal cells in AD brains; and (ii) translocated I2PP2A colocalized not only with the PP2A catalytic subunit, but also with phosphorylated tau in neuronal cytoplasm. Furthermore, according to preliminary data, the cleavage site of I2PP2A is located between amino acids 175 and 176 of the I2PP2A sequence. Because the sequence from amino acids 168 to 181 on I2PP2A presumably functions as a nuclear localization signal (NLS), inhibition of break down of the NLS in I2PP2A is expected to be a novel therapeutic target for the treatment of Alzheimer’s disease.
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阿尔茨海默氏病的GSK3假设。
影响因子：
4.7
作者：
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通讯作者：
Lovestone S
影响因子：
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作者：
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通讯作者：
Anderton, BH
影响因子：
5.3
作者：
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通讯作者：
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影响因子：
2
作者：
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通讯作者：
Takeda, Masatoshi
影响因子：
2
作者：
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通讯作者：
Kamijima, Kunitoshi