Caenorhabditis elegans hub genes that respond to amyloid beta are homologs of genes involved in human Alzheimer’s disease

Rasoul Godini, Roger Pocock, Hossein Fallahi

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The prominent characteristic of Alzheimer’s disease (AD) is the accumulation of amyloid beta (Abeta) proteins in the form of plaques that cause molecular and cellular alterations in the brain. Due to the paucity of brain samples of early-stage Abeta aggregation, animal models have been developed to study early events in AD. Caenorhabditis elegans is a genetically tractable animal model for AD. Here, we used transcriptomic data, network-based protein-protein interactions and weighted gene co-expression network analysis (WGCNA), to detect modules and their gene ontology in response to Abeta aggregation in C. elegans. Additionally, hub genes and their orthologues in human and mouse were identified to study their relation to AD. We also found several transcription factors (TFs) responding to Abeta accumulation. Our results show that Abeta expression in C. elegans relates to general processes such as molting cycle, locomotion, and larval development plus AD-associated processes, including protein phosphorylation, and G-protein coupled receptor-regulated pathways. We reveal that many hub genes and TFs including ttbk-2, daf-16, and unc-49 have human and mouse orthologues that are directly or potentially associated with AD and neural development. In conclusion, using systems biology we identified important genes and biological processes in C. elegans that respond to Abeta aggregation, which could be used as potential diagnostic or therapeutic targets. In addition, because of evolutionary relationship to AD in human, we suggest that C. elegans is a useful model for studying early molecular events in AD.

Original languageEnglish
Article numbere0219486
Number of pages28
JournalPLoS ONE
Volume14
Issue number7
DOIs
Publication statusPublished - 10 Jul 2019

Keywords

  • alzheimer's disease
  • caenorhabditis elegans
  • gene expression
  • neuronal differentiation
  • neuronal dendrites
  • neuronal morphology
  • DNA-binding proteins
  • membrane receptor signaling

Cite this

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title = "Caenorhabditis elegans hub genes that respond to amyloid beta are homologs of genes involved in human Alzheimer’s disease",
abstract = "The prominent characteristic of Alzheimer’s disease (AD) is the accumulation of amyloid beta (Abeta) proteins in the form of plaques that cause molecular and cellular alterations in the brain. Due to the paucity of brain samples of early-stage Abeta aggregation, animal models have been developed to study early events in AD. Caenorhabditis elegans is a genetically tractable animal model for AD. Here, we used transcriptomic data, network-based protein-protein interactions and weighted gene co-expression network analysis (WGCNA), to detect modules and their gene ontology in response to Abeta aggregation in C. elegans. Additionally, hub genes and their orthologues in human and mouse were identified to study their relation to AD. We also found several transcription factors (TFs) responding to Abeta accumulation. Our results show that Abeta expression in C. elegans relates to general processes such as molting cycle, locomotion, and larval development plus AD-associated processes, including protein phosphorylation, and G-protein coupled receptor-regulated pathways. We reveal that many hub genes and TFs including ttbk-2, daf-16, and unc-49 have human and mouse orthologues that are directly or potentially associated with AD and neural development. In conclusion, using systems biology we identified important genes and biological processes in C. elegans that respond to Abeta aggregation, which could be used as potential diagnostic or therapeutic targets. In addition, because of evolutionary relationship to AD in human, we suggest that C. elegans is a useful model for studying early molecular events in AD.",
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Caenorhabditis elegans hub genes that respond to amyloid beta are homologs of genes involved in human Alzheimer’s disease. / Godini, Rasoul; Pocock, Roger; Fallahi, Hossein.

In: PLoS ONE, Vol. 14, No. 7, e0219486, 10.07.2019.

Research output: Contribution to journalArticleResearchpeer-review

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