Effects of DISC1 on Alzheimer's disease cell models assessed by iTRAQ proteomics analysis. Issue 1 (28th January 2022)

• Record Type: Journal Article
• Authors: Lu, Jiajie; Huang, Rihong; Peng, Yuecheng; Wang, Haojian; Feng, Zejia; Fan, Yongyang; Zeng, Zhaorong; Wang, Yezhong; Wei, Jiana; Wang, Zhaotao
• Is Part Of: Bioscience reports. Volume 42:Issue 1(2022)
• Publication Date: 2022-01-28
• Subjects: Alzheimer's disease (AD) -- DISC1 -- iTRAQ proteomic; Molecular biology -- Periodicals; Cytology -- Periodicals; 572.8
• DOI: 10.1042/BSR20211150
• Languages: English
• ISSNs: 0144-8463

Abstract

Abstract: 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 DISC1 high 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.