Proteasome inhibition increases tau accumulation independent of phosphorylation
Proteasome inhibition increases tau accumulation independent of phosphorylation
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DOI：
10.1016/j.neurobiolaging.2008.02.012
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发表时间：
2009-12-01
影响因子：
4.2
通讯作者：
Wang, Jian-Zhi
中科院分区：
文献类型：
--
作者：
Liu, Ying-Hua;Wei, Wei;Wang, Jian-Zhi
在阿尔茨海默病（AD）发作中，蛋白酶体和tau蛋白降解之间存在内在联系，然而，蛋白酶体在tau蛋白水解中的作用仍不确定。本实验研究了蛋白酶体抑制对大鼠tau蛋白积累、磷酸化、泛素化、溶解度及记忆保留的影响。我们观察到乳酸蛋白酶抑制了蛋白酶体的活性，增加了不同tau物种的水平和不溶性，包括磷酸化的tau。磷酸化tau蛋白W的升高；在归一化为总tau蛋白后，pS214和pT231 tau蛋白的水平甚至低于正常水平。蛋白酶体的抑制导致camp依赖性蛋白激酶、糖原合成酶激酶-3 β和周期蛋白依赖性激酶-5的激活。我们得出结论，蛋白酶体的抑制增加了tau蛋白的积累和不溶解性，而不依赖于tau蛋白的磷酸化，JNK的抑制可能是大鼠大脑中tau蛋白磷酸化相对降低的部分原因。(C) 2008 Elsevier Inc .版权所有
An intrinsic link between proteasome and tau degradation in Alzheimer's disease (AD) hits been suggested, however, the role of proteasome in the proteolysis of tau is still uncertain. Here, we investigated the influence of proteasome inhibition oil the accumulation, phosphorylation, ubiquitination, solubility of tau and the memory retention in rats. We observed that lactacystin inhibited the proteasome activities and increased the level and insolubility of different tau species, including phosphorylated tau. The elevation of the phosphorylated tau W;Is no longer present and the level of pS214 and pT231 tau was even lower than normal level after normalized to total tau Inhibition of proteasome resulted in activation of cAMP-dependent protein kinase, glycogen synthase kinases-3 beta and cyclin-dependent kinase-5, and inhibition of protein phosphatase-2A and c-Jun N-terminal kinase (JNK) Proteasome inhibition did not affect the memory retention of the rate We conclude that proteasome inhibition increases accumulation and insolubility of tau proteins independent of tau phosphorylation, and JNK inhibition may be partially responsible for the relatively decreased phosphorylation of tau in the rat brains. (C) 2008 Elsevier Inc All rights reserved