Neurodegenerative disorders: insights from the nematode Caenorhabditis elegans.

Neurodegenerative diseases impose a burden on society, yet for the most part, the mechanisms underlying neuronal dysfunction and death in these disorders remain unclear despite the identification of relevant disease genes. Given the molecular conservation in neuronal signaling pathways across vertebrate and invertebrate species, many researchers have turned to the nematode Caenorhabditis elegans to identify the mechanisms underlying neurodegenerative disease pathology. C. elegans can be engineered to express human proteins associated with neurodegeneration; additionally, the function of C. elegans orthologs of human neurodegenerative disease genes can be dissected. Herein, we examine major C. elegans neurodegeneration models that recapitulate many aspects of human neurodegenerative disease and we survey the screens that have identified modifier genes. This review highlights how the C. elegans community has used this versatile organism to model several aspects of human neurodegeneration and how these studies have contributed to our understanding of human disease. (c) 2010 Elsevier Inc. All rights reserved.