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@ARTICLE{Moens:276275,
author = {Moens, Thomas G and Da Cruz, Sandrine and Neumann, Manuela
and Shelkovnikova, Tatyana A and Shneider, Neil A and Van
Den Bosch, Ludo},
title = {{A}myotrophic lateral sclerosis caused by {FUS} mutations:
advances with broad implications.},
journal = {The lancet},
volume = {24},
number = {2},
issn = {1474-4422},
address = {London},
publisher = {Lancet Publ. Group},
reportid = {DZNE-2025-00254},
pages = {166 - 178},
year = {2025},
abstract = {Autosomal dominant mutations in the gene encoding the DNA
and RNA binding protein FUS are a cause of amyotrophic
lateral sclerosis (ALS), and about $0·3-0·9\%$ of patients
with ALS are FUS mutation carriers. FUS-mutation-associated
ALS (FUS-ALS) is characterised by early onset and rapid
progression, compared with other forms of ALS. However,
different pathogenic mutations in FUS can result in markedly
different age at symptom onset and rate of disease
progression. Most FUS mutations disrupt its nuclear
localisation, leading to its cytoplasmic accumulation in the
CNS. FUS also forms inclusions in around $5\%$ of patients
with the related neurodegenerative condition frontotemporal
dementia. However, there are key differences between the two
diseases at the genetic and neuropathological level, which
suggest distinct pathogenic processes. Experimental models
have uncovered potential pathogenic mechanisms in FUS-ALS
and informed therapeutic strategies that are currently in
development, including the silencing of FUS expression using
an intrathecally administered antisense oligonucleotide.},
subtyp = {Review Article},
keywords = {Amyotrophic Lateral Sclerosis: genetics / Humans /
RNA-Binding Protein FUS: genetics / Mutation: genetics /
Animals / RNA-Binding Protein FUS (NLM Chemicals) / FUS
protein, human (NLM Chemicals)},
cin = {AG Neumann},
ddc = {610},
cid = {I:(DE-2719)1210003},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39862884},
doi = {10.1016/S1474-4422(24)00517-9},
url = {https://pub.dzne.de/record/276275},
}