Alzheimer's Disease Drug Discovery: In-vivo screening using C. elegans as a model for β-amyloid peptide-induced toxicity.

Alzheimer's disease (AD) is a complex human neurodegenerative disease. Currently the therapeutics for AD only treat the symptoms. While numbers of excellent studies have used mammalian models to discover new compounds, the time and effort involved with screening large numbers of candidates is prohibitive. Cultured mammalian neurons are of often used to perform high through-put screens (HTS) however, cell culture lacks the organismal complexity involved in AD. To address these issues a number of researchers are turning to the round worm, C. elegans. C. elegans has numerous models of both Tau and Aβ induced toxicity; the two prime components observed to correlate with AD pathology. These models have lead to the discovery of numerous AD modulating candidates. Further, the ease of performing RNAi for any gene in the C. elegans genome allows for identification of proteins involved in the mechanism of drug action. These attributes make C. elegans well positioned to aid in the discovery of new AD therapies.