Age-dependent shift in the de novo proteome accompanies pathogenesis in an Alzheimer's disease mouse model.
Age-dependent shift in the de novo proteome accompanies pathogenesis in an Alzheimer's disease mouse model.
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DOI：
10.1038/s42003-021-02324-6
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发表时间：
2021-06-30
影响因子：
5.9
通讯作者：
Klann E
中科院分区：
文献类型：
--
作者：
Elder MK;Erdjument-Bromage H;Oliveira MM;Mamcarz M;Neubert TA;Klann E
阿尔茨海默病 (AD) 是一种与年龄相关的神经退行性疾病，与记忆丧失有关，但与 AD 相关的神经病理变化早在记忆障碍发生前数年就开始了。对 AD 早期分子异常的研究可能为在发病前针对记忆障碍提供创新机会。蛋白质合成减少在 AD 中起着重要作用，但这种细胞功能失调的后果仍不清楚。我们假设从头蛋白质组的改变驱动了海马体的早期代谢改变，这种改变在整个 AD 进展过程中持续存在。使用组合氨基酸标记方法选择性标记和富集新合成的蛋白质，我们发现年轻 APP/PS1 小鼠的从头蛋白质组在症状出现前受到干扰，影响突触、溶酶体和线粒体途径的多种成分的合成。此外，核糖体亚基大簇的合成在整个发育过程中受到影响。我们的数据表明，蛋白质合成的大规模变化可能是 AD 细胞功能障碍的基础。埃尔德等人。研究了年轻 APP/PS1 阿尔茨海默病模型小鼠的分离海马切片中的从头蛋白质组，发现蛋白质合成的大规模变化先于症状出现。这些结果表明，蛋白质合成的广泛失调可能导致阿尔茨海默病的细胞功能障碍。
Alzheimer’s disease (AD) is an age-related neurodegenerative disorder associated with memory loss, but the AD-associated neuropathological changes begin years before memory impairments. Investigation of the early molecular abnormalities in AD might offer innovative opportunities to target memory impairment prior to onset. Decreased protein synthesis plays a fundamental role in AD, yet the consequences of this dysregulation for cellular function remain unknown. We hypothesize that alterations in the de novo proteome drive early metabolic alterations in the hippocampus that persist throughout AD progression. Using a combinatorial amino acid tagging approach to selectively label and enrich newly synthesized proteins, we found that the de novo proteome is disturbed in young APP/PS1 mice prior to symptom onset, affecting the synthesis of multiple components of the synaptic, lysosomal, and mitochondrial pathways. Furthermore, the synthesis of large clusters of ribosomal subunits were affected throughout development. Our data suggest that large-scale changes in protein synthesis could underlie cellular dysfunction in AD. Elder et al. investigated the de novo proteome in isolated hippocampal slices of young APP/PS1 Alzheimer’s model mice and revealed that large-scale changes in protein synthesis precede symptom onset. These results suggest that broad dysregulation of protein synthesis could contribute toward cellular dysfunction in Alzheimer’s disease.
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影响因子：
--
作者：
Bo H;Kang W;Jiang N;Wang X;Zhang Y;Ji LL
通讯作者：
Ji LL
影响因子：
4.7
作者：
Bowling H;Bhattacharya A;Zhang G;Lebowitz JZ;Alam D;Smith PT;Kirshenbaum K;Neubert TA;Vogel C;Chao MV;Klann E
通讯作者：
Klann E
影响因子：
6.1
作者：
Chevere-Torres, Itzamarie;Kaphzan, Hanoch;Bhattacharya, Aditi;Kang, Areum;Maki, Jordan M.;Gambello, Michael J.;Arbiser, Jack L.;Santini, Emanuela;Klann, Eric
通讯作者：
Klann, Eric
DOI：
10.1046/j.1365-2990.2002.t01-1-00410.x
发表时间：
2002-12-01
影响因子：
5
作者：
Ferrer, I
通讯作者：
Ferrer, I
影响因子：
7.3
作者：
Bowling H;Zhang G;Bhattacharya A;Pérez-Cuesta LM;Deinhardt K;Hoeffer CA;Neubert TA;Gan WB;Klann E;Chao MV
通讯作者：
Chao MV