Transgenic C. elegans as a Model in Alzheimers Research

Author(s): Yanjue Wu, Yuan Luo

Journal Name: Current Alzheimer Research

Volume 2 , Issue 1 , 2005

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Alzheimers disease (AD) has been associated with aggregation of β-amyloid peptide (Aβ) and cell death in the brain. Using various models, such as the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster and the mouse Mus musculus, investigators have attempted to imitate the pathology process of AD for better understanding of the cellular mechanisms and for possible therapeutic intervention. Among many in vitro and in vivo models of AD, transgenic C. elegans expressing human Aβ has shown its own advantages. The transgenic C. elegans model have been used in studying AD due to its short life span, facility to maintain, ability to develop muscle-associated deposits reactive to amyloid-specific dyes and the concomitant progressive paralysis phenotype. Moreover, the transgenic C. elegans exhibits increased levels of reactive oxygen species (ROS) and protein carbonyls, similar to those observed in AD patients, supporting the current theory on Aβ-induced oxidative stress and subsequent neurodegeneration in AD. DNA microarray assays of the worm demonstrated several stress-related genes being upregulated, particularly two genes homologous to human αB-crystallin and tumor necrosis factor-related protein, which were also upregulated in postmortem AD brain. Studies in our laboratory along with others suggest that the transgenic C. elegans model is a suitable in vivo model to relate Aβ-expression with its toxicity, which may underlie AD pathology. It may also be used as a tool for pharmacological evaluation of novel therapeutic agents.

Keywords: caenorhabditis elegans, amyloid, alzheimers disease

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Article Details

Year: 2005
Page: [37 - 45]
Pages: 9
DOI: 10.2174/1567205052772768

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PDF: 146