Watching worms whither: modeling neurodegeneration in C. elegans

Caenorhabditis elegans is increasingly being used to study neurodegenerative diseases. Nematodes are translucent, which facilitates study of particular neurons in the living animal, and easy to manipulate genetically. Despite vast evolutionary divergence, human proteins are functionally active when expressed in C. elegans, and disease-linked mutations in these proteins also cause phenotypic changes in the nematode. In this chapter, we review use of C. elegans to investigate the pathophysiology of Alzheimer's disease, Parkinson's disease, and axonal degeneration. Studies of presenilin, β-amyloid, tau, α-synuclein, and LRRK2 all produce strong phenotypic effects in C. elegans, and in many cases reproduce selective neuronal vulnerability observed in humans. Disease-linked mutations enhance degeneration in the C. elegans models. These studies are increasingly leading to high-throughput screens that identify novel genes and novel pharmaceuticals that modify the disease course.