Caspase-3- and calpain-mediated tau cleavage are differentially prevented by estrogen and testosterone in beta-amyloid-treated hippocampal neurons
Caspase-3- and calpain-mediated tau cleavage are differentially prevented by estrogen and testosterone in beta-amyloid-treated hippocampal neurons
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DOI：
10.1016/j.neuroscience.2006.09.012
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发表时间：
2007-01-05
期刊：
影响因子：
3.3
通讯作者：
Ferreira, A.
中科院分区：
文献类型：
--
作者：
Park, S. -Y.;Tournell, C.;Ferreira, A.
越来越多的证据表明，微管相关蛋白tau（神经原纤维缠结的主要成分）的蛋白水解切割可能在β-淀粉样蛋白（A β）诱导的中枢神经元神经毒性的分子机制中发挥作用。在本研究中，我们分析了性激素是否可以阻止这种tau蛋白裂解，从而保护大鼠海马神经元免受A β毒性。我们的研究结果表明，雌激素和睾酮阻止caspase-3和calpain介导的tau蛋白裂解，分别。因此，雌激素降低了半胱天冬酶-3切割的50 kDa截短的tau蛋白的水平，而睾酮阻止了钙蛋白酶切割的17 kDa tau蛋白片段的产生。此外，我们的结果表明，这些tau蛋白水解形式的水平的降低伴随着A β处理的神经元中细胞存活率的增加。此外，我们的研究结果表明，睾酮比雌激素更有效地保护海马神经元免受A β诱导的细胞死亡。总的来说，我们的数据表明，防止与正常衰老相关的雌激素和睾酮的下降可能会降低中枢神经元对A β诱导的毒性的敏感性。(c)2006年IBRO。由爱思唯尔有限公司出版。保留所有权利。
A growing body of evidence suggests that the proteolytic cleavage of the microtubule-associated protein tau, the main component of neurofibrillary tangles, might play a role in the molecular mechanisms underlying beta-amyloid (A beta)-induced neurotoxicity in central neurons. In the present study, we analyzed whether sex hormones could prevent such tau cleavage, and hence, protect rat hippocampal neurons against A beta toxicity. Our results indicated that estrogen and testosterone prevented caspase-3- and calpainmediated tau cleavage, respectively. Thus, estrogen decreased the levels of caspase-3-cleaved 50-kDa truncated tau, while testosterone prevented the generation of a calpain-cleaved 17-kDa tau fragment. In addition, our results showed that the decrease in the levels of these tau proteolytic forms was accompanied by an increased cell survival in A beta-treated neurons. Furthermore, our findings indicated that testosterone was more effective than estrogen in protecting hippocampal neurons against A beta-induced cell death. Collectively, our data suggest that preventing the decline of estrogen and testosterone associated with normal aging might reduce the susceptibility of central neurons to A beta-induced toxicity. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.