A C. elegans model for neurodegeneration in Cockayne syndrome.
Amanda F C Lopes, Katarzyna Bozek, Marija Herholz, Aleksandra Trifunovic, Matthias Rieckher, Björn Schumacher
Author Information
Amanda F C Lopes: Institute for Genome Stability in Aging and Disease, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.
Katarzyna Bozek: Center for Molecular Medicine (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Robert-Koch-Str. 21, 50931 Cologne, Germany.
Marija Herholz: Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.
Aleksandra Trifunovic: Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.
Matthias Rieckher: Institute for Genome Stability in Aging and Disease, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.
Björn Schumacher: Institute for Genome Stability in Aging and Disease, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.
Cockayne syndrome (CS) is a congenital syndrome characterized by growth and mental retardation, and premature ageing. The complexity of CS and mammalian models warrants simpler metazoan models that display CS-like phenotypes that could be studied in the context of a live organism. Here, we provide a characterization of neuronal and mitochondrial aberrations caused by a mutation in the csb-1 gene in Caenorhabditis elegans. We report a progressive neurodegeneration in adult animals that is enhanced upon UV-induced DNA damage. The csb-1 mutants show dysfunctional hyperfused mitochondria that degrade upon DNA damage, resulting in diminished respiratory activity. Our data support the role of endogenous DNA damage as a driving factor of CS-related neuropathology and underline the role of mitochondrial dysfunction in the disease.
