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@ARTICLE{Voigt:136092,
author = {Voigt, Aaron and Herholz, David and Fiesel, Fabienne C and
Kaur, Kavita and Müller, Daniel and Karsten, Peter and
Weber, Stephanie S and Kahle, Phillip and Marquardt, Till
and Schulz, Jörg B},
title = {{TDP}-43-mediated neuron loss in vivo requires
{RNA}-binding activity.},
journal = {PLOS ONE},
volume = {5},
number = {8},
issn = {1932-6203},
address = {San Francisco, California, US},
publisher = {PLOS},
reportid = {DZNE-2020-02414},
pages = {e12247},
year = {2010},
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.},
keywords = {Amyotrophic Lateral Sclerosis: genetics / Animals / Cell
Line / Chickens: genetics / Chickens: metabolism / Chickens:
physiology / DNA-Binding Proteins: genetics / DNA-Binding
Proteins: metabolism / Drosophila melanogaster: cytology /
Drosophila melanogaster: genetics / Drosophila melanogaster:
metabolism / Drosophila melanogaster: physiology /
Frontotemporal Lobar Degeneration: genetics / Gene
Expression Regulation / Humans / Intracellular Space:
metabolism / Locomotion / Longevity / Male / Motor Neurons:
metabolism / Mutation / Neurons: cytology / Neurons:
metabolism / Organ Specificity / Protein Binding / Protein
Transport / RNA: metabolism / DNA-Binding Proteins (NLM
Chemicals) / RNA (NLM Chemicals)},
cin = {AG Krauß / AG Kahle 2 / Tübingen Pre 2020},
ddc = {610},
cid = {I:(DE-2719)1011006 / I:(DE-2719)1210000-4 /
I:(DE-2719)6000018},
pnm = {345 - Population Studies and Genetics (POF3-345) / 342 -
Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-345 / G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:20806063},
pmc = {pmc:PMC2923622},
doi = {10.1371/journal.pone.0012247},
url = {https://pub.dzne.de/record/136092},
}