Journal Article (Review Article)

DZNE-2025-00254

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Amyotrophic lateral sclerosis caused by FUS mutations: advances with broad implications.

Moens, T. G. ; Da Cruz, S. ; Neumann, M.DZNE* ; Shelkovnikova, T. A. ; Shneider, N. A. ; Van Den Bosch, L.

2025
Lancet Publ. Group London

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Please use a persistent id in citations: doi:10.1016/S1474-4422(24)00517-9

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.

Keyword(s): Amyotrophic Lateral Sclerosis: genetics (MeSH) ; Humans (MeSH) ; RNA-Binding Protein FUS: genetics (MeSH) ; Mutation: genetics (MeSH) ; Animals (MeSH) ; RNA-Binding Protein FUS ; FUS protein, human

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Contributing Institute(s):

1. Molecular Neuropathology of Neurodegenerative Diseases (AG Neumann)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2025

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 40 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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