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https://hdl.handle.net/2440/75895
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Type: | Journal article |
Title: | Utility of an improved model of amyloid-beta (Aβ₁₋₄₂) toxicity in Caenorhabditis elegans for drug screening for Alzheimer’s disease |
Other Titles: | Utility of an improved model of amyloid-beta (A beta(1-42)) toxicity in Caenorhabditis elegans for drug screening for Alzheimer's disease |
Author: | McColl, G. Roberts, B. Pukala, T. Kenche, V. Roberts, C. Link, C. Ryan, T. Masters, C. Barnham, K. Bush, A. Cherny, R. |
Citation: | Molecular Neurodegeneration, 2012; 7(1):1-9 |
Publisher: | BioMed Central Ltd |
Issue Date: | 2012 |
ISSN: | 1750-1326 1750-1326 |
Statement of Responsibility: | Gawain McColl, Blaine R Roberts, Tara L Pukala, Vijaya B Kenche, Christine M Roberts, Christopher D Link, Timothy M Ryan, Colin L Masters, Kevin J Barnham, Ashley I Bush, and Robert A Cherny |
Abstract: | Background: The definitive indicator of Alzheimer’s disease (AD) pathology is the profuse accumulation of amyloid-ß (Aß) within the brain. Various in vitro and cell-based models have been proposed for high throughput drug screening for potential therapeutic benefit in diseases of protein misfolding. Caenorhabditis elegans offers a convenient in vivo system for examination of Aß accumulation and toxicity in a complex multicellular organism. Ease of culturing and a short life cycle make this animal model well suited to rapid screening of candidate compounds. Results: We have generated a new transgenic strain of C. elegans that expresses full length Aß1-42. This strain differs from existing Aß models that predominantly express amino-truncated Aß3-42. The Aß1-42 is expressed in body wall muscle cells, where it oligomerizes, aggregates and results in severe, and fully penetrant, age progressive-paralysis. The in vivo accumulation of Aß1-42 also stains positive for amyloid dyes, consistent with in vivo fibril formation. The utility of this model for identification of potential protective compounds was examined using the investigational Alzheimer’s therapeutic PBT2, shown to be neuroprotective in mouse models of AD and significantly improve cognition in AD patients. We observed that treatment with PBT2 provided rapid and significant protection against the Aß-induced toxicity in C. elegans. Conclusion: This C. elegans model of full length Aß1-42 expression can now be adopted for use in screens to rapidly identify and assist in development of potential therapeutics and to study underlying toxic mechanism(s) of Aß. |
Keywords: | Amyloid beta peptide alzheimer’s disease caenorhabditis elegans 8-hydroxyquinoline PBT2 and drug screen |
Description: | The electronic version of this article is the complete one and can be found online at: http://www.molecularneurodegeneration.com/content/7/1/57 Extent: 9p. |
Rights: | © 2012 McColl et al.; licensee BioMed Central Ltd.This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
DOI: | 10.1186/1750-1326-7-57 |
Published version: | http://dx.doi.org/10.1186/1750-1326-7-57 |
Appears in Collections: | Aurora harvest 4 IPAS publications |
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File | Description | Size | Format | |
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hdl_75895.pdf | Published version | 1.66 MB | Adobe PDF | View/Open |
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