Effects of DISC1 on Alzheimer's disease cell models assessed by iTRAQ proteomics analysis.
Effects of DISC1 on Alzheimer's disease cell models assessed by iTRAQ proteomics analysis.
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通过 iTRAQ 蛋白质组学分析评估 DISC1 对阿尔茨海默病细胞模型的影响。
DOI：
10.1042/bsr20211150
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发表时间：
2022-01-28
影响因子：
4
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Lu J;Huang R;Peng Y;Wang H;Feng Z;Fan Y;Zeng Z;Wang Y;Wei J;Wang Z
阿尔茨海默病（AD）是一种老年人神经退行性疾病，目前尚无治愈方法。在之前的研究中，我们发现AD大脑中精神分裂症1型支架蛋白（DISC1）被下调，DISC1的异位表达可以通过保护突触可塑性和下调BACE1来延缓AD的进展。然而，其根本机制仍有待阐明。在本研究中，我们使用同量异序标签进行相对和绝对定量 (iTRAQ) 和质谱 (MS) 比较了表达淀粉样前体蛋白 (APP) 的正常 AD 细胞和 DISC1high AD 细胞的蛋白质组。鉴定了差异表达蛋白 (DEP)，并构建了蛋白质-蛋白质相互作用 (PPI) 网络来鉴定 DISC1 的相互作用伙伴。根据相互作用评分，NDE1、GRM3、PTGER3 和 KATNA1 被确定为与 DISC1 功能或物理相关，因此可能调节 AD 的发展。 DEP 通过 DAVID 软件通过基因本体论 (GO) 和京都基因和基因组百科全书 (KEGG) 数据库进行功能注释，并使用非监督直系同源群 (eggNOG) 数据库来确定它们的进化关系。 DEP 在微管和线粒体相关途径中显着富集。进行基因集富集分析 (GSEA) 来识别 DISC1 过表达时激活的基因和通路。我们的研究结果为 AD 中 DISC1 功能的调控机制提供了新的见解。
Alzheimer’s disease (AD) is a form of neurodegenerative disease in the elderly with no cure at present. In a previous study, we found that the scaffold protein, disrupted in Schizophrenia 1 (DISC1) is down-regulated in the AD brains, and ectopic expression of DISC1 can delay the progression of AD by protecting synaptic plasticity and down-regulating BACE1. However, the underlying mechanisms remain not to be elucidated. In the present study, we compared the proteomes of normal and DISC1high AD cells expressing the amyloid precursor protein (APP) using isobaric tag for relative and absolute quantitation (iTRAQ) and mass spectrometry (MS). The differentially expressed proteins (DEPs) were identified, and the protein–protein interaction (PPI) network was constructed to identify the interacting partners of DISC1. Based on the interaction scores, NDE1, GRM3, PTGER3 and KATNA1 were identified as functionally or physically related to DISC1, and may therefore regulate AD development. The DEPs were functionally annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases with the DAVID software, and the Non-supervised Orthologous Groups (eggNOG) database was used to determine their evolutionary relationships. The DEPs were significantly enriched in microtubules and mitochondria-related pathways. Gene set enrichment analysis (GSEA) was performed to identify genes and pathways that are activated when DISC1 is overexpressed. Our findings provide novel insights into the regulatory mechanisms underlying DISC1 function in AD.