Decreased RNA, and increased RNA oxidation, in ribosomes from early Alzheimer's disease
Decreased RNA, and increased RNA oxidation, in ribosomes from early Alzheimer's disease
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DOI：
10.1007/s11064-006-9071-5
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发表时间：
2006-05-01
影响因子：
4.4
通讯作者：
Keller, Jeffrey N.
中科院分区：
文献类型：
--
作者：
Ding, Qunxing;Markesbery, William R.;Keller, Jeffrey N.
所有细胞都依赖于有效的蛋白质合成来维持细胞内稳态。我们实验室最近的研究表明，蛋白质合成和核糖体功能的下降发生在阿尔茨海默病（AD）的最早阶段。其他研究表明，核糖体RNA氧化作为AD中蛋白质合成减少的潜在介体的潜在作用。核糖体是蛋白质和核酸的复合体，介导所有蛋白质合成。目前尚不清楚在AD的进展过程中核糖体复合物内是否发生核糖体RNA的显著改变。在这项研究中，我们检查了核糖体RNA的量在不同的核糖体组分产生的对照组，轻度认知障碍（MCI）的个人，和个人与AD。在每例受试者的顶下小叶中进行研究。总之，这些数据表明，在AD的进展过程中，核糖体复合物内的核糖体RNA的量总体下降。此外，这些研究为MCI和AD的核糖体复合物内RNA氧化的总体升高提供了证据。总之，这些数据强烈表明核糖体内的RNA改变作为MCI和AD中蛋白质合成减少的介体的作用。
All cells rely on efficient protein synthesis in order to maintain cellular homeostasis. Recent studies from our laboratory indicate that declines in protein synthesis and ribosome function occur in the earliest stage of Alzheimer's disease (AD). Additional studies indicate a potential role for ribosomal RNA oxidation as a potential mediator of decreased protein synthesis in AD. The ribosome is a complex of proteins and nucleic acids that mediates all protein synthesis. At present it is unclear if significant alterations in ribosomal RNA occurs within the ribosome complex during the progression of AD. In this study we examined the amount of ribosomal RNA in the different ribosomal fractions generated from control subjects, individuals with mild cognitive impairment (MCI), and individuals with AD. Studies were conducted in the inferior parietal lobule of each subject. Together, these data demonstrate that during the progression of AD there is a gross decline in the amount of ribosomal RNA within the ribosome complex. Additionally, these studies provide evidence for gross elevations in RNA oxidation within the ribosome complex of MCI and AD. Together, these data strongly suggest a role for RNA alterations within the ribosome as a mediator of decreased protein synthesis in both MCI and AD.