Lassen Pernille S, Thygesen Camilla, Larsen Martin R, Kempf Stefan J
Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense, Denmark.
Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense, Denmark; Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark.
J Proteomics. 2017 May 24;161:11-25. doi: 10.1016/j.jprot.2017.04.003. Epub 2017 Apr 8.
Phosphorylation and glycosylation are important protein modifications in the mammalian brain acting as drivers of neural development, neurotransmission signalling and neurite elongation as well as synaptic morphology. Despite their important functional roles in the brain, only a few studies have elucidated them in neurodegenerative diseases such as Alzheimer's disease. Here, we comprehensively review Alzheimer's pathology in relation to protein phosphorylation and glycosylation on synaptic plasticity from neuroproteomics data. Moreover, we highlight several mass spectrometry-based sample processing technologies including an in-house developed TiO-SIMAC-TiO-based enrichment protocol to isolate and enrich phosphorylated and glycosylated peptides enabling to elucidate hopefully new early disease biomarkers.
磷酸化和糖基化是哺乳动物大脑中重要的蛋白质修饰，它们驱动神经发育、神经传递信号、神经突伸长以及突触形态形成。尽管它们在大脑中具有重要的功能作用，但仅有少数研究在诸如阿尔茨海默病等神经退行性疾病中对其进行了阐明。在此，我们依据神经蛋白质组学数据，全面综述了与突触可塑性相关的蛋白质磷酸化和糖基化方面的阿尔茨海默病病理学。此外，我们重点介绍了几种基于质谱的样品处理技术，包括一种内部开发的基于TiO-SIMAC-TiO的富集方案，用于分离和富集磷酸化和糖基化肽段，有望借此阐明新的早期疾病生物标志物。
