|
Motor neuron atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
Amyotrophic lateral sclerosis (ALS) is a lethal disease characterized by motor neuron degeneration and associated with aggregation of nuclear RNA-binding proteins (RBPs), including FUS.
|
30937520 |
2019 |
|
Motor neuron atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
Our study demonstrates that vascular regression occurs before motor neuron degeneration in FUS (1-359) mice, and highlights that heterogeneity in responses to novel ALS therapeutics can already be detected in preclinical mouse models of ALS.This article has an associated First Person interview with the joint first authors of the paper.
|
31383794 |
2019 |
|
Motor neuron atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
We have previously reported dose and age-dependent motor neuron degeneration in transgenic mice overexpressing human wild-type FUS, resulting in a motor phenotype detected by ∼28 days and death by ∼100 days.
|
29194538 |
2018 |
|
Motor neuron atrophy
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Humanized mutant FUS drives progressive motor neuron degeneration without aggregation in 'FUSDelta14' knockin mice.
|
29053787 |
2017 |
|
Motor neuron atrophy
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
FUS loss-of-function and toxic gain-of-function mechanisms have been proposed to explain how mutant FUS leads to motor neuron degeneration, but neither has been firmly established in the pathogenesis of ALS.
|
26842965 |
2016 |
|
Motor neuron atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
Moreover, using protein mass spectrometry, we identified a group of RNA-binding proteins (including FUS, a protein critically involved in motor neuron degeneration) that interacted with LRSAM1.
|
27615052 |
2016 |
|
Motor neuron atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
It is unclear whether FUS depletion from the nucleus or FUS inclusions in the cytoplasm triggers motor neuron degeneration.
|
26123490 |
2015 |
|
Motor neuron atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
These findings support a two-hit hypothesis, whereby cytoplasmic mislocalization of FUS protein, followed by cellular stress, contributes to the formation of cytoplasmic aggregates that may sequester FUS, disrupt RNA processing and initiate motor neuron degeneration.
|
23474818 |
2013 |
|
Motor neuron atrophy
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
The molecular mechanisms through which mutant TDP-43 and FUS may cause motor neuron degeneration are not well understood.
|
23559573 |
2013 |
|
Motor neuron atrophy
|
0.100 |
Biomarker
|
disease |
BEFREE |
Overexpression of human wild-type FUS causes progressive motor neuron degeneration in an age- and dose-dependent fashion.
|
22961620 |
2013 |
|
Motor neuron atrophy
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
However, it is not clear how mutations of Fus lead to motor neuron degeneration in ALS.
|
22443542 |
2012 |
|
Motor neuron atrophy
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
We have generated Caenorhabditis elegans and zebrafish animal models expressing mutant human TDP-43 (A315T or G348C) or FUS (S57Δ or R521H) that reflect certain aspects of ALS including motor neuron degeneration, axonal deficits, and progressive paralysis.
|
22848727 |
2012 |
|
Motor neuron atrophy
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Mutations in the RNA-binding protein FUS (fused in sarcoma) are linked to amyotrophic lateral sclerosis (ALS), but the mechanism by which these mutants cause motor neuron degeneration is not known.
|
20699327 |
2010 |
|
Motor neuron atrophy
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
FUS is involved in the regulation of transcription and RNA splicing and transport, and it has functional homology to another ALS gene, TARDBP, which suggests that a common mechanism may underlie motor neuron degeneration.
|
19251628 |
2009 |