TDP-43-mediated neuron loss in vivo requires RNA-binding activity.
2010 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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- Authors
- Voigt, Aaron ; Herholz, David; Fiesel, Fabienne C.; Kaur, Kavita; Müller, Daniel ; Karsten, Peter; Weber, Stephanie S.; Kahle, Philipp J.; Marquardt, Till ; Schulz, Jörg
- 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 isoforms via same-site gene insertion and neural expression in Drosophila; followed by transposon-based motor neuron-specific transgenesis in a chick vertebrate system. Using this bi-systemic approach we uncovered a requirement of inherent TDP-43 RNA-binding function--but not ALS/FTLD-linked mutation, mislocalization, or truncation--for TDP-43-mediated neurotoxicity in vivo.
- Issue Date
- 2010
- Journal
- PloS one
- ISSN
- 1932-6203
- Language
- English