title: Caenorhabditis elegans as a model system for studying non-cell-autonomous mechanisms in protein-misfolding diseases.
abstract: Caenorhabditis elegans has a number of distinct advantages that are useful for understanding the basis for cellular and organismal dysfunction underlying age-associated diseases of protein misfolding. Although protein aggregation, a key feature of human neurodegenerative diseases, has been typically explored in vivo at the single-cell level using cells in culture, there is now increasing evidence that proteotoxicity has a non-cell-autonomous component and is communicated between cells and tissues in a multicellular organism. These discoveries have opened up new avenues for the use of C. elegans as an ideal animal model system to study non-cell-autonomous proteotoxicity, prion-like propagation of aggregation-prone proteins, and the organismal regulation of stress responses and proteostasis. This Review focuses on recent evidence that C. elegans has mechanisms to transmit certain classes of toxic proteins between tissues and a complex stress response that integrates and coordinates signals from single cells and tissues across the organism. These findings emphasize the potential of C. elegans to provide insights into non-cell-autonomous proteotoxic mechanisms underlying age-related protein-misfolding diseases.
authors.affiliation: Department of Molecular Biosciences, Rice Institute for Biomedical Research, Northwestern University, 2205 Tech Drive, Evanston, IL 60208, USA.
authors.forename: Carmen I
authors.initials: CI
authors.lastname: Nussbaum-Krammer
authors.forename: Richard I
authors.initials: RI
authors.lastname: Morimoto
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D019636:Neurodegenerative Diseases / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D011328:Prions / Q000378:metabolism; D011489:Protein Denaturation; D017510:Protein Folding; D011506:Proteins / Q000378:metabolism; D057165:Proteostasis Deficiencies / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D011328:Prions; D011506:Proteins
keywords: Caenorhabditis elegans; Cell non-autonomous proteotoxicity; Prion-like spreading