Impaired proteasome function in Alzheimer's disease
Impaired proteasome function in Alzheimer's disease
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DOI：
10.1046/j.1471-4159.2000.0750436.x
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发表时间：
2000-07-01
影响因子：
4.7
通讯作者：
Markesbery, WR
中科院分区：
文献类型：
--
作者：
Keller, JN;Hanni, KB;Markesbery, WR
蛋白酶体活性的抑制足以诱导神经元变性和死亡;然而，在神经退行性疾病中蛋白酶体活性的改变尚未得到证实。在本研究中，我们分析了16例阿尔茨海默病（AD）和9例年龄和性别匹配的对照组的短死后间隔尸检大脑中的蛋白酶体活性。AD患者海马及海马旁回（48%）、颞上级回、颞中回（38%）、顶下小叶（28%）蛋白酶体活性较对照组明显降低。相反。在枕叶或小脑中均未观察到蛋白酶体活性的显著降低。蛋白酶体活性的丧失与蛋白酶体表达的减少无关，这表明蛋白酶体在AD中可能受到翻译后修饰的抑制。一起这些数据表明蛋白酶体抑制在与AD相关的神经变性中的可能作用。
Inhibition of proteasome activity is sufficient to induce neuron degeneration and death; however, altered proteasome activity in a neurodegenerative disorder has not been demonstrated. In the present study, we analyzed proteasome activity in short-postmortem-interval autopsied brains from 16 Alzheimer's disease (AD) and nine age- and sex-matched controls. A significant decrease tn proteasome activity was observed in the hippocampus and parahippocampal gyrus (48%), superior and middle temporal gyri (38%), and inferior parietal lobule (28%) of AD patients compared with controls. In contrast. no significant decrease in proteasome activity was observed in either the occipital lobe or the cerebellum. The loss of proteasome activity was not associated with a decrease in proteasome expression, suggesting that the proteasome may become inhibited in AD by a posttranslational modification. Together. these data indicate a possible role for proteasome inhibition in the neurodegeneration associated with AD.