title: Gains or losses: molecular mechanisms of TDP43-mediated neurodegeneration.
abstract: RNA-binding proteins, and in particular TAR DNA-binding protein 43 (TDP43), are central to the pathogenesis of motor neuron diseases and related neurodegenerative disorders. Studies on human tissue have implicated several possible mechanisms of disease and experimental studies are now attempting to determine whether TDP43-mediated neurodegeneration results from a gain or a loss of function of the protein. In addition, the distinct possibility of pleotropic or combined effects - in which gains of toxic properties and losses of normal TDP43 functions act together - needs to be considered.
authors: Translational Neuropathology Research Laboratory, Division of Neuropathology, Department of Pathology and Laboratory Medicine, University of Pennsylvania, 605B Stellar Chance Laboratories, 422 Curie Boulevard, Philadelphia, Pennsylvania                 19104, USA.
authors: Edward B
authors: EB
authors: Lee
authors: Virginia M-Y
authors: VM
authors: Lee
authors: John Q
authors: JQ
authors: Trojanowski
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000502:physiology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D016601:RNA-Binding Proteins