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Hippocampus Proteomics and Brain Lipidomics Reveal Network Dysfunction and Lipid Molecular Abnormalities in APP/PS1 Mouse Model of Alzheimer's Disease.
Journal of Proteome Research ( IF 4.4 ) Pub Date : 2020-06-08 , DOI: 10.1021/acs.jproteome.0c00255
Xueju Zhang 1, 2 , Weiwei Liu 3 , Yan Cao 1, 2 , Wen Tan 2, 3
Affiliation  

Alzheimer’s disease (AD) is closely associated with protein dysfunction and aberrant lipid metabolism in the brain. Our study could be conducive to the discovery of lipid and protein biomarkers for early diagnosis and therapy. In our current work, novel quantitative proteomic and lipidomic methods were developed for the characterization of molecular perturbation occurring in the brain in early stage AD mice. For this purpose, we performed a proteomic and lipidomic screening by liquid chromatography with mass spectrometry. Significant changes were detected, including 231 proteins and 11 lipid compounds in the AD mouse brain. Early stage AD disturbed biological pathways implicated in neuroactive ligand–receptor, complement and coagulation cascades, PI3K-Akt signaling and metabolic pathways, and glycerophospholipid metabolism. The results in the current study suggest that these significantly altered proteins and lipids may be implicated in early stage AD. Our work raises the possibility of AD diagnosis and therapy by providing new protein targets and lipid biomarkers.

中文翻译:

海马蛋白质组学和脑脂质组学揭示阿尔茨海默病 APP/PS1 小鼠模型中的网络功能障碍和脂质分子异常。

阿尔茨海默病 (AD) 与大脑中的蛋白质功能障碍和脂质代谢异常密切相关。我们的研究可能有助于发现用于早期诊断和治疗的脂质和蛋白质生物标志物。在我们目前的工作中,开发了新的定量蛋白质组学和脂质组学方法,用于表征早期 AD 小鼠大脑中发生的分子扰动。为此,我们通过液相色谱和质谱进行了蛋白质组学和脂质组学筛选。检测到显着变化,包括 AD 小鼠大脑中的 231 种蛋白质和 11 种脂质化合物。早期 AD 扰乱了与神经活性配体受体、补体和凝血级联反应、PI3K-Akt 信号传导和代谢途径以及甘油磷脂代谢有关的生物学途径。目前研究的结果表明,这些显着改变的蛋白质和脂质可能与早期 AD 有牵连。我们的工作通过提供新的蛋白质靶标和脂质生物标志物提高了 AD 诊断和治疗的可能性。
更新日期:2020-08-08
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