Exploring the conservation of Alzheimer-related pathways between H. sapiens and C. elegans: a network alignment approach

Avgi E Apostolakou,Vassiliki A Iconomidou,Georgia I Nasi,Xhuliana K Sula,Katerina C Nastou

doi:10.1038/s41598-021-83892-9

Abstract

Alzheimer disease (AD) is a neurodegenerative disorder with an –as of yet– unclear etiology and pathogenesis. Research to unveil disease processes underlying AD often relies on the use of neurodegenerative disease model organisms, such as Caenorhabditis elegans. This study sought to identify biological pathways implicated in AD that are conserved in Homo sapiens and C. elegans. Protein–protein interaction networks were assembled for amyloid precursor protein (APP) and Tau in H. sapiens—two proteins whose aggregation is a hallmark in AD—and their orthologs APL-1 and PTL-1 for C. elegans. Global network alignment was used to compare these networks and determine similar, likely conserved, network regions. This comparison revealed that two prominent pathways, the APP-processing and the Tau-phosphorylation pathways, are highly conserved in both organisms. While the majority of interactions between proteins in those pathways are known to be associated with AD in human, they remain unexamined in C. elegans, signifying the need for their further investigation. In this work, we have highlighted conserved interactions related to AD in humans and have identified specific proteins that can act as targets for experimental studies in C. elegans, aiming to uncover the underlying mechanisms of AD.

Highlights

Alzheimer disease (AD) is a neurodegenerative disorder with an –as of yet– unclear etiology and pathogenesis
The aim of this work was to explore both of these concepts in the context of comparing homologous PPI networks in H. sapiens and C. elegans to uncover conserved pathways between these organisms that could be exploited for the study of AD
Failure to construct a network with data from IntAct, led to the use of STRING instead, and the final C. elegans network used in this study consists of 51 proteins and 69 PPIs (Fig. 1)

Summary

Introduction

Alzheimer disease (AD) is a neurodegenerative disorder with an –as of yet– unclear etiology and pathogenesis. We have highlighted conserved interactions related to AD in humans and have identified specific proteins that can act as targets for experimental studies in C. elegans, aiming to uncover the underlying mechanisms of AD. C. elegans does not possess an ortholog for β-secretase, and has no β-secretase activity[10] For this reason, many transgenic C. elegans strains that express human Aβ and Tau sequences in specific cell types have been c reated[10,13] and are used as models for the study of AD and other neurodegenerative diseases. Previous studies[21,22] have used PPI networks to explore AD mechanisms using the model organism C. elegans To our awareness this is the first effort to employ network alignment for the transfer of knowledge between C. elegans and human for the study of this disease

Objectives

Methods

Results

Conclusion