[Alzheimer disease and tau protein].
[Alzheimer disease and tau protein].
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[阿尔茨海默病和 tau 蛋白]。
DOI：
10.5692/clinicalneurol.52.1171
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
M. Takeda
中科院分区：
文献类型：
--
作者：
Toshihisa Tanaka;Daisuke Mayuyama;M. Takeda
为了阐明tau蛋白在阿尔茨海默病和相关疾病的神经退行性过程中的参与，研究了tau蛋白的自组装过程和降解过程。了解tau蛋白聚集的机制，tau蛋白与14-3-3蛋白的结合亲和力，将tau蛋白转化为丝状或聚集形式。采用表面等离子体共振测定法进行研究。蛋白激酶A对tau的磷酸化增加了tau对14-3-3的亲和力，而磷酸化减弱了细丝或聚集体的形成。与野生型未磷酸化tau相比，FTDP-17突变增加了未磷酸化tau对14-3-3的亲和力。然而，磷酸化使其亲和力进一步增加至与磷酸化野生型tau的亲和力相似的水平。类似地，磷酸化也减弱了FTDP-17突变tau的细丝或聚集体的形成。为了了解细胞内积累的机制，研究了蛋白酶的可能参与。在几种蛋白酶中，嘌呤霉素敏感的氨肽酶（PSA）被发现是tau蛋白降解的主要调节剂。此外，FTDP-17突变增加了细胞中tau蛋白的磷酸化，并减弱了tau蛋白的细胞内降解。这些结果表明tau蛋白的自组装和积累受磷酸化调节，FTDP-17突变影响这些复杂的过程。
To elucidate involvement of tau protein in neurodegenerative processes in Alzheimer disease and related disorders, self-assembly process and degradative process of tau protein were examined. To understand the mechanisms of the aggregation, binding affinity of tau protein to 14-3-3 protein, which converts tau to a filamentous or aggregated form. was investigated employing a surface plasmon resonance assay. Phosphorylation of tau by protein kinase A increased affinity of tau to 14-3-3, whereas the phosphorylation attenuated formation of filaments or aggregates. FTDP-17 mutation increased affinity of unphosphorlated tau to 14-3-3, compared to wild typed unphosphorylated tau. However the phosphorylation increased its affinity further to the similar level of the affinity of phosphorylated wild typed tau. Similarly the phosphorylation also attenuated formation of filaments or aggreeagates from FTDP-17 mutated tau. To understand the mechanisms of the intracellular accumulation, possible involvement of proteases were studied. Among several proteases, puromycin-sensitive aminopeptidase (PSA) was found as a predominant regulator of degradation of tau protein. In addition FTDP-17 mutation increased phosphorylation of tau proten in cells, and attenuated intracellular degradation of tau protein. These results suggest that self-assembly and accumulation of tau protein are regulated by phosphorylation, and FTDP-17 mutation affects those complexed processes.
影响因子：
4.7
作者：
Sadik, Golam;Tanaka, Toshihisa;Takeda, Masatoshi
通讯作者：
Takeda, Masatoshi
嘌呤霉素敏感氨肽酶参与培养细胞中 tau 蛋白的蛋白水解，以及与 17 号染色体 (FTDP-17) 突变 tau 相关的额颞叶痴呆和帕金森病的蛋白水解减弱
影响因子：
2
作者：
Kentarou Yanagi;Toshihisa Tanaka;Kiyoko Kato;G. Sadik;T. Morihara;T. Kudo;M. Takeda
通讯作者：
M. Takeda