“The Greatness of the Smallest Ones”: The Most Valuable Attributes of Flies and Worms for the Study of Neurodegeneration

Over the last decades, a large number of experimental models have been developed to explore the mechanisms underlying neurodegenerative disorders. Invertebrate models of neurodegeneration, such as the fruit fly Drosophila melanogaster and the nematode Caenorhabtidis elegans, have emerged as successful complementary systems to mammalian models, facilitating identification of relevant pathways and novel diseaseassociated genes. These organisms provide reliable systems for identifying genetic modifiers of neuropathologies and the interesting possibility of screening and testing potential drugs for treatments to prevent and/or alleviate disease symptoms.

This chapter will focus on the main experimental strategies used in Drosophila melanogaster and Caenorhabtidis elegans to study neurodegeneration. Insights from forward genetic approaches, transgenic models of human neurodegenerative disorders and studies of fly/worm homologs of human disease genes will be presented. The value of using invertebrate models for the study of neurodegeneration will be discussed, highlighting advantages and limitations associated with these studies.

Keywords: Alzheimer’s disease, Caenorhabtidis elegans, Drosophila melanogaster, drug screening, forward genetics, fruit flies, genetic enhancers, genetic screen, genetic suppressors, Huntington’s disease, invertebrate models, neurodegenerative diseases, neurodegeneration, neuronal death, Parkinson’s disease, Polyglutamine diseases, reverse genetics, transgenic models, worms.