Identifying Aβ-specific pathogenic mechanisms using a nematode model of Alzheimer's disease. Neurobiol Aging 2015 Feb;36(2):857-66
Date
12/03/2014Pubmed ID
25457027Pubmed Central ID
PMC4315719DOI
10.1016/j.neurobiolaging.2014.10.016Scopus ID
2-s2.0-84922790072 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
Multiple gene expression alterations have been linked to Alzheimer's disease (AD), implicating multiple metabolic pathways in its pathogenesis. However, a clear distinction between AD-specific gene expression changes and those resulting from nonspecific responses to toxic aggregating proteins has not been made. We investigated alterations in gene expression induced by human beta-amyloid peptide (Aβ) in a Caenorhabditis elegans AD model. Aβ-induced gene expression alterations were compared with those caused by a synthetic aggregating protein to identify Aβ-specific effects. Both Aβ-specific and nonspecific alterations were observed. Among Aβ-specific genes were those involved in aging, proteasome function, and mitochondrial function. An intriguing observation was the significant overlap between gene expression changes induced by Aβ and those induced by Cry5B, a bacterial pore-forming toxin. This led us to hypothesize that Aβ exerts its toxic effect, at least in part, by causing damage to biological membranes. We provide in vivo evidence consistent with this hypothesis. This study distinguishes between Aβ-specific and nonspecific mechanisms and provides potential targets for therapeutics discovery.
Author List
Hassan WM, Dostal V, Huemann BN, Yerg JE, Link CDMESH terms used to index this publication - Major topics in bold
AgingAlzheimer Disease
Amyloid beta-Peptides
Animals
Bacterial Proteins
Caenorhabditis elegans
Disease Models, Animal
Endotoxins
Gene Expression
Hemolysin Proteins
Humans
Mitochondria
Molecular Targeted Therapy
Proteasome Endopeptidase Complex
