Dataset Information

Energy crisis precedes global metabolic failure in a novel Caenorhabditis elegans Alzheimer Disease model.

ABSTRACT: Alzheimer Disease (AD) is a progressive neurological disorder characterized by the deposition of amyloid beta (Aβ), predominantly the Aβ_1-42 form, in the brain. Mitochondrial dysfunction and impaired energy metabolism are important components of AD pathogenesis. However, the causal and temporal relationships between them and AD pathology remain unclear. Using a novel C. elegans AD strain with constitutive neuronal Aβ_1-42 expression that displays neuromuscular defects and age-dependent behavioural dysfunction reminiscent of AD, we have shown that mitochondrial bioenergetic deficit is an early event in AD pathogenesis, preceding dysfunction of mitochondrial electron transfer chain (ETC) complexes and the onset of global metabolic failure. These results are consistent with an emerging view that AD may be a metabolic neurodegenerative disease, and also confirm that Aβ-driven metabolic and mitochondrial effects can be reproduced in organisms separated by large evolutionary distances.

SUBMITTER: Fong S

PROVIDER: S-EPMC5031964 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Energy crisis precedes global metabolic failure in a novel Caenorhabditis elegans Alzheimer Disease model.

Fong Sheng S Teo Emelyne E Ng Li Fang LF Chen Ce-Belle CB Lakshmanan Lakshmi Narayanan LN Tsoi Sau Yee SY Moore Philip Keith PK Inoue Takao T Halliwell Barry B Gruber Jan J

Scientific reports 20160922

Alzheimer Disease (AD) is a progressive neurological disorder characterized by the deposition of amyloid beta (Aβ), predominantly the Aβ<sub>1-42</sub> form, in the brain. Mitochondrial dysfunction and impaired energy metabolism are important components of AD pathogenesis. However, the causal and temporal relationships between them and AD pathology remain unclear. Using a novel C. elegans AD strain with constitutive neuronal Aβ<sub>1-42</sub> expression that displays neuromuscular defects and ag ...[more]

PMID: 27653553

Similar Datasets

Project description:Understanding gene function and genetic relationships is fundamental to our efforts to better understand biological systems. Previous studies systematically describing genetic interactions on a global scale have either focused on core biological processes in protozoans or surveyed catastrophic interactions in metazoans. Here, we describe a reliable high-throughput approach capable of revealing both weak and strong genetic interactions in the nematode Caenorhabditis elegans.We investigated interactions between 11 'query' mutants in conserved signal transduction pathways and hundreds of 'target' genes compromised by RNA interference (RNAi). Mutant-RNAi combinations that grew more slowly than controls were identified, and genetic interactions inferred through an unbiased global analysis of the interaction matrix. A network of 1,246 interactions was uncovered, establishing the largest metazoan genetic-interaction network to date. We refer to this approach as systematic genetic interaction analysis (SGI). To investigate how genetic interactions connect genes on a global scale, we superimposed the SGI network on existing networks of physical, genetic, phenotypic and coexpression interactions. We identified 56 putative functional modules within the superimposed network, one of which regulates fat accumulation and is coordinated by interactions with bar-1(ga80), which encodes a homolog of beta-catenin. We also discovered that SGI interactions link distinct subnetworks on a global scale. Finally, we showed that the properties of genetic networks are conserved between C. elegans and Saccharomyces cerevisiae, but that the connectivity of interactions within the current networks is not.Synthetic genetic interactions may reveal redundancy among functional modules on a global scale, which is a previously unappreciated level of organization within metazoan systems. Although the buffering between functional modules may differ between species, studying these differences may provide insight into the evolution of divergent form and function.

Dataset Information

Energy crisis precedes global metabolic failure in a novel Caenorhabditis elegans Alzheimer Disease model.

Publications

Energy crisis precedes global metabolic failure in a novel Caenorhabditis elegans Alzheimer Disease model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets