Sequential expression of cell-cycle regulators and Alzheimer's disease-related proteins in entorhinal cortex after hippocampal excitotoxic damage
Sequential expression of cell-cycle regulators and Alzheimer's disease-related proteins in entorhinal cortex after hippocampal excitotoxic damage
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DOI：
10.1002/jnr.21301
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发表时间：
2007-06-01
影响因子：
4.2
通讯作者：
Arias, Clorinda
中科院分区：
文献类型：
--
作者：
Hernandez-Ortega, Karina;Ferrera, Patricia;Arias, Clorinda
越来越多的证据表明，阿尔茨海默病 (AD) 神经元变性的最早事件之一是有丝分裂后神经元的异常细胞周期激活，事实上，这可能足以引发神经退行性级联反应。在本研究中，我们检查了细胞周期蛋白和细胞周期蛋白依赖性激酶（通常与细胞周期控制相关的分子）是否可能参与海马兴奋性毒性损伤后两个相互关联的区域（内嗅皮层（EC）和齿状回（DG））中改变的阿尔茨海默病蛋白的延迟表达。在红藻氨酸引起海马神经元死亡后，发现 EC 中 G 期、S 期甚至 G(2) 期的几种细胞周期蛋白上调。此外，我们描述了两种阿尔茨海默病相关蛋白 PHF-1 和 APP 的渐进表达，它们在 G/S 期标记物增加后立即达到更高水平。因此，本研究的结果支持细胞周期失调作为该过程的关键组成部分，当该区域的突触输入的目标位点因兴奋性毒性损伤而受损时，该过程可能最终导致该区域的 AD 蛋白表达和神经元死亡。 (c) 2007 年 Wiley-Liss, Inc.
Growing evidence suggests that one of the earliest events in the neuronal degeneration of Alzheimer's disease (AD) is aberrant cell-cycle activation in postmitotic neurons, which may, in fact, be sufficient to initiate the neurodegenerative cascade. In the present study we examined whether cyclins and cyclin-dependent kinases, molecules normally associated with cell-cycle control, may be involved in delayed expression of altered Alzheimer's proteins in two interconnected areas, the entorhinal cortex (EC) and the dentate gyrus (DG), after a hippocampal excitotoxic lesion. Several cell-cycle proteins of the G, and S phases and even of the G(2) phase were found to be up-regulated in the EC after kainic acid evoked neuronal death in the hippocampus. In addition, we describe the progressive expression of two Alzheimer's-related proteins, PHF-1 and APP, which reached higher levels immediately after the increase in G,/S-phase markers. Hence,,the results of the present study support the participation of cell-, cycle dysregulation as a key component of the process that may ultimately lead to expression of, AD proteins and neuronal death in a brain area when the target site for synaptic inputs in that area is damaged by an excitotoxic insult. (c) 2007 Wiley-Liss, Inc.