ArticleActa neuropathologica2019
FUS pathology in ALS is linked to alterations in multiple ALS-associated proteins and rescued by drugs stimulating autophagy.
Article in Acta neuropathologica, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 129 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Article
- Nuclear dysfunction in aging and neurodegeneration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Human FUS is toxic via association with RNA polymerase II in Drosophila.Cell death & disease · 2026Article
- MicroRNAs and Long Non-Coding RNAs Affect the Mechanisms Involved in Age-Related Neurodegeneration in a Manner Depending on RNA-Binding Proteins.Molecular neurobiology · 2026Review
- Review
- Comparative CRISPRi screens reveal a human stem cell dependence on mRNA translation-coupled quality control.Nature structural & molecular biology · 2025Article
- ALS-associated RNA-binding proteins promote UNC13A transcription through REST downregulation.The EMBO journal · 2025Article
- Neuroaxonal Degeneration as a Converging Mechanism in Motor Neuron Diseases (MNDs): Molecular Insights into RNA Dysregulation and Emerging Therapeutic Targets.International journal of molecular sciences · 2025Review
- Organ-Specific Small Protein Networks in 100 kDa Ultrafiltrates: Functional Analysis and Implications for Neuroregenerative Medicine.International journal of molecular sciences · 2025Article
- Fisetin Attenuates Mutant SOD1 Aggregation in Amyotrophic Lateral Sclerosis via Nrf2-Mediated Autophagy Activation.Journal of molecular neuroscience : MN · 2025Article
- RNA-binding proteins in ALS and FTD: from pathogenic mechanisms to therapeutic insights.Molecular neurodegeneration · 2025Review
- Exploring Protein Misfolding in Amyotrophic Lateral Sclerosis: Structural and Functional Insights.Biomedicines · 2025Review
- Loss of age-associated increase in mbioRxiv : the preprint server for biology · 2025Article
- Cytoplasmic accumulation of a splice variant of hnRNPA2/B1 contributes to FUS-associated toxicity in a mouse model of ALS.Cell death & disease · 2025Article
- Pharmacological effects, molecular mechanisms and strategies to improve bioavailability of curcumin in the treatment of neurodegenerative diseases.Frontiers in pharmacology · 2025Review
- An Overview of Liquid-Liquid Phase Separation and Its Mechanisms in Sepsis.Journal of inflammation research · 2025Review
- HuD impairs neuromuscular junctions and induces apoptosis in human iPSC and Drosophila ALS models.Nature communications · 2024Article
- Regulation of DNA damage response by RNA/DNA-binding proteins: Implications for neurological disorders and aging.Ageing research reviews · 2024Review
- KIF1A, R1457Q, and P1688L Mutations Induce Protein Abnormal Aggregation and Autophagy Impairment in iPSC-Derived Motor Neurons.Biomedicines · 2024Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
28 authors at 8 institutions in 4 countries.
Funding
Abstract
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. How FUS aggregation and neurodegeneration are prevented in healthy motor neurons remain critically unanswered questions. Here, we use a combination of ALS patient autopsy tissue and induced pluripotent stem cell-derived neurons to study the effects of FUS mutations on RBP homeostasis. We show that FUS' tendency to aggregate is normally buffered by interacting RBPs, but this buffering is lost when FUS mislocalizes to the cytoplasm due to ALS mutations. The presence of aggregation-prone FUS in the cytoplasm causes imbalances in RBP homeostasis that exacerbate neurodegeneration. However, enhancing autophagy using small molecules reduces cytoplasmic FUS, restores RBP homeostasis and rescues motor function in vivo. We conclude that disruption of RBP homeostasis plays a critical role in FUS-ALS and can be treated by stimulating autophagy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.