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

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 DISC1 is downregulated 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 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.

Unified epigenomic, transcriptomic, proteomic, and metabolomic taxonomy of Alzheimer’s disease progression and heterogeneity

“…Gene PFKP is related with impaired neuronal glucose metabolism observed in AD ( 26 ). With an abnormal methylation level here, gene DISC1 is commonly associated with schizophrenia, but its ectopic (out of place) expression has been suggested to delay the progression of AD by protecting synaptic plasticity and down-regulating BACE1 ( 27 ). Protein 77G7 is a monoclonal antibody with the capacity to recognize tau filament cores ( 28 ).…”

Transcriptional profiles in olfactory pathway–associated brain regions of African green monkeys: Associations with age and Alzheimer's disease neuropathology

“…Critically, in culture, a variant of VPS4A causes accumulation of both Aβ and tau, 50 suggesting a possible causal role in AD. As for POLDIP3 and TYW1B , both have been identified previously as directly or indirectly associated with neurodegenerative diseases 51,52 . POLDIP3 (aka SKAR , S6 kinase 1 (S6K1) Aly/REF‐like target) mRNA splicing is regulated by transactive response DNA‐binding protein‐43 (TDP‐43), 53 an RNA splicing co‐factor that contributes to regulation of translation and cell size and has been linked to neurotoxicity, amyotrophic lateral sclerosis, and frontotemporal lobar degeneration 54 .…”

FTX271: A potential gene resource for plant antiviral transgenic breeding

“…To accurately identify the functions of the differentially expressed proteins, GSEA (Gene Set Enrichment Analysis) was used ( Lu et al, 2022 ). GSEA (4.0.3) is a software developed by the Broad Institute for analyzing pathways enriched by differentially expressed proteins that can scan all pathways, intuitively understanding the difference of all proteins in each pathway, while it does not depend on the p value cutoff of differential expression.…”