Interdisciplinary Program in Neuroscience, School of Systems Biology, George Mason University, Fairfax, VA 22030, USA.
School of Systems Biology, George Mason University, Manassas VA 20110, USA.
Cells. 2021 Sep 10;10(9):2380. doi: 10.3390/cells10092380.
Alzheimer's disease (AD) is marked by chronic neurodegeneration associated with the occurrence of plaques containing amyloid β (Aβ) proteins in various parts of the human brain. An increase in several Aβ fragments is well documented in patients with AD and anti-amyloid targeting is an emerging area of therapy. Soluble Aβ can bind to various cell surface and intracellular molecules with the pathogenic Aβ fragment leading to neurotoxicity. Here we examined the effect of Aβ on network adaptations in the proteome of nerve growth factor (NGF) differentiated PC12 cells using liquid-chromatography electrospray ionization mass spectrometry (LC-ESI MS/MS) proteomics. Whole-cell peptide mass fingerprinting was coupled to bioinformatic gene set enrichment analysis (GSEA) in order to identify differentially represented proteins and related gene ontology (GO) pathways within Aβ treated cells. Our results underscore a role for Aβ in disrupting proteome responses for signaling, bioenergetics, and morphology in mitochondria. These findings highlight the specific components of the mitochondrial response during Aβ neurotoxicity and suggest several new biomarkers for detection and surveillance of amyloid disease.
阿尔茨海默病（AD）的特征是慢性神经退行性变，与人类大脑各个部位含有淀粉样β（Aβ）蛋白的斑块的发生有关。AD 患者中几种 Aβ 片段的增加已有充分记录，针对淀粉样蛋白的靶向治疗是一个新兴的治疗领域。可溶性 Aβ 可以与各种细胞表面和细胞内分子结合，导致致病性 Aβ 片段导致神经毒性。在这里，我们使用液相色谱-电喷雾电离质谱（LC-ESI MS/MS）蛋白质组学研究了 Aβ 对神经生长因子（NGF）分化的 PC12 细胞蛋白质组中网络适应的影响。对全细胞肽质量指纹图谱进行了生物信息学基因集富集分析（GSEA），以鉴定 Aβ 处理细胞中差异表达的蛋白质及其相关基因本体论（GO）途径。我们的结果强调了 Aβ 在破坏信号转导、生物能量和线粒体形态的蛋白质组反应中的作用。这些发现突出了 Aβ 神经毒性期间线粒体反应的特定组成部分，并为淀粉样蛋白疾病的检测和监测提供了几个新的生物标志物。
