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. 2022 Jan 28;42(1):BSR20211150.
doi: 10.1042/BSR20211150.

Effects of DISC1 on Alzheimer's disease cell models assessed by iTRAQ proteomics analysis

Jiajie Lu  1 , Rihong Huang  1 , Yuecheng Peng  1 , Haojian Wang  1 , Zejia Feng  1 , Yongyang Fan  1 , Zhaorong Zeng  1 , Yezhong Wang  1 , Jiana Wei  2 , Zhaotao Wang  1
Affiliations

Effects of DISC1 on Alzheimer's disease cell models assessed by iTRAQ proteomics analysis

Jiajie Lu et al. Biosci Rep. .

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 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.

Keywords: Alzheimer’s disease (AD); DISC1; iTRAQ proteomic.

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Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1
Figure 1. Schematic representation of the experimental design
Figure 2
Figure 2. PPI network of DEPs
(A) The PPI network of DEPs was constructed by STRING and Cytoscape. Red nodes indicate up-regulated genes, green nodes indicate down-regulated genes. The node size correlates to the degree of connectivity and line thickness with interaction score. DISC1 is marked in purple in the upper left corner. (B) Proteins with physical or functional association with DISC1.
Figure 3
Figure 3. The enrichment analysis of DEPs
Functional enrichment analysis of GO (A). Functional enrichment analysis of KEGG (B). Functional enrichment analysis of eggNOG (C).
Figure 4
Figure 4. Enrichment plots from GSEA in DISC1high phenotype
GSEA results showing DEPs in BP (A), MF (B), CC (C) and REACTOME (D). All results of GSEA were based on NES, adjusted P-value and FDR value.
See this image and copyright information in PMC

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