tdp-43-mediated neuron loss in vivo requires rna-binding activitytdp-43-mediated神经元损失体内需要rna结合的活动.pdfVIP

TDP-43-Mediated Neuron Loss In Vivo Requires RNA-Binding Activity 1. 2. 3. 1 ¨ 2 1 Aaron Voigt , David Herholz , Fabienne C. Fiesel , Kavita Kaur , Daniel Muller , Peter Karsten , 3 3 2 ¨ 1,4 Stephanie S. Weber , Philipp J. Kahle , Till Marquardt *, Jorg B. Schulz * 1 Department of Neurology, University Medical Center, RWTH Aachen, Aachen, Germany, 2 Developmental Neurobiology Laboratory, European Neuroscience Institute- ¨ ¨ Gottingen, Gottingen, Germany, 3 Laboratory of Functional Neurogenetics, Department of Neurodegeneration, Hertie Institute for Clinical Brain Research and German ¨ ¨ ¨ Center for Neurodegenerative Diseases, Tubingen, Germany, 4 JARA Brain (Julich-Aachen-Research-Alliance), Julich, Germany Abstract Alteration and/or mutations of the ribonucleoprotein TDP-43 have been firmly linked to human neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). The relative impacts of TDP-43 alteration, mutation, or inherent protein function on neural integrity, however, remain less clear—a situation confounded by conflicting reports based on transient and/or random-insertion transgenic expression. We therefore performed a stringent comparative investigation of impacts of these TDP-43 modifications on neural integrity in vivo. To achieve this, we systematically screened ALS/FTLD-associated and synthetic TDP-43 is