Oxidative damage and amyloid-β metabolism in brain regions of the longest-lived rodents.
Oxidative damage and amyloid-β metabolism in brain regions of the longest-lived rodents.
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DOI：
10.1002/jnr.23320
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发表时间：
2014-02
影响因子：
4.2
通讯作者：
Buffenstein R
中科院分区：
文献类型：
--
作者：
Edrey YH;Oddo S;Cornelius C;Caccamo A;Calabrese V;Buffenstein R
裸鼹鼠 (NMR) 是最长寿的啮齿动物，年轻个体的大脑中 Aβ 含量很高。这项研究的目的有两个：评估 NMR 大脑关键区域（皮层、海马、小脑）中 Aβ 的分布，并了解 Aβ 的积累是由于生成增加还是降解减少所致。最近的证据表明，脂质过氧化物直接参与细胞保护蛋白的诱导，例如热休克蛋白（Hsps），其在应激耐受的细胞机制中发挥核心作用。因此，在关键的 NMR 大脑区域评估了淀粉样蛋白前体蛋白加工、脂质过氧化、热休克蛋白、氧化还原状态和蛋白质降解过程。与小鼠相比，NMR 大脑具有较高水平的脂质过氧化，并且 NMR 海马具有最高水平的 Aβ 毒性最强的部分（可溶性 Aβ1-42）。这不是由于 Aβ 产量增加，而是由于抗氧化潜力较低，而抗氧化潜力与 Hsp70 和血红素加氧酶 1 的诱导较低以及泛素蛋白酶体活性较低有关。因此，NMR 可以作为理解氧化应激和 Aβ 水平之间的关系及其对大脑影响的自然模型。
Naked mole rats (NMRs) are the longest-lived rodents, with young individuals having high levels of Aβ in their brains. The purpose of this study was twofold: to assess the distribution of Aβ in key regions of NMR brains (cortex, hippocampus, cerebellum) and to understand whether the accumulation of Aβ is due to enhanced production or decreased degradation. Recent evidence indicates that lipid peroxides directly participate in induction of cytoprotective proteins, such as heat shock proteins (Hsps), which play a central role in the cellular mechanisms of stress tolerance. Amyloid precursor protein processing, lipid peroxidation, Hsps, redox status, and protein degradation processes were therefore assessed in key NMR brain regions. NMR brains had high levels of lipid peroxidation compared with mice, and the NMR hippocampus had the highest levels of the most toxic moiety of Aβ (soluble Aβ1–42). This was due not to increased Aβ production but rather to low antioxidant potential, which was associated with low induction of Hsp70 and heme oxygenase-1 as well as low ubiquitin-proteasome activity. NMRs may therefore serve as natural models for understanding the relationship between oxidative stress and Aβ levels and its effects on the brain.