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通过与人类迟发性阿尔茨海默病比较评估动物模型。

Evaluation of Animal Models by Comparison with Human Late-Onset Alzheimer's Disease.

机构信息

Herbal Medicine Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 34054, Republic of Korea.

College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Republic of Korea.

出版信息

Mol Neurobiol. 2018 Dec;55(12):9234-9250. doi: 10.1007/s12035-018-1036-6. Epub 2018 Apr 14.

Abstract

Despite many efforts to alleviate the pathological conditions of Alzheimer's disease (AD), effective therapeutic drugs have not been developed, mainly because of the lack of molecular information about AD and animal models. We observed the reciprocal regulation of AD-associated genes (AD genes) and their related functions. Upregulated AD genes were positioned in central regions in the protein-protein interaction network and were involved in inflammation and DNA repair pathways. Downregulated AD genes positioned in the periphery of the network were associated with metabolic pathways. Using these features of AD genes, we found that 5×FAD, amyloid β-injected mice, and rats in the initial phases after bilateral common carotid artery occlusion (BCCAO) exhibited patterns that were most similar to those of AD. In contrast, using differentially expressed genes from animal models, we observed that 3×Tg and animals in late phases of BCCAO were positioned close to AD genes.

摘要

尽管人们做出了许多努力来减轻阿尔茨海默病(AD)的病理状况,但仍未开发出有效的治疗药物,主要是因为缺乏有关 AD 的分子信息和动物模型。我们观察到与 AD 相关的基因(AD 基因)及其相关功能的相互调节。上调的 AD 基因在蛋白质-蛋白质相互作用网络的中央区域定位,并参与炎症和 DNA 修复途径。下调的 AD 基因位于网络的外围,与代谢途径有关。利用 AD 基因的这些特征,我们发现 5×FAD、β-淀粉样蛋白注射的小鼠以及双侧颈总动脉闭塞(BCCAO)后早期的大鼠表现出与 AD 最相似的模式。相比之下,使用动物模型中的差异表达基因,我们观察到 3×Tg 和 BCCAO 晚期的动物与 AD 基因接近。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c41f/6208860/d00cf83bf826/12035_2018_1036_Fig1_HTML.jpg

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