ArticleNature communications2025
Single-cell RNA-sequencing reveals early mitochondrial dysfunction unique to motor neurons shared across FUS- and TARDBP-ALS.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it.
- What can we learn on ALS pathophysiology from iPSC-derived motor neurons harbouring TARBDP mutations: a systematic review.Translational neurodegeneration · 2026Pooled it
- Dysregulation of mitochondrial bioenergetics, RNA processing, and cellular stress responses in FUS-ALS: a multi-dataset transcriptomic perspective.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- Interpretable machine learning enables de novo mapping of cell type-specific RNA splicing regulation from scRNA-seq data.Nature communications · 2026Article
- Review
- Review
- Mitochondrial Dysfunction: From Molecular Mechanisms to Modern Approaches for Basic and Clinical Research.Biomedicines · 2026Review
- Karyoptosis mediates cell death and neurodegeneration upon proteotoxic stress.Nature communications · 2026Article
- Hyperglycemia impairs cognitive function by inducing mitochondrial damage through lactylation of LRPPRC at K223.EMBO molecular medicine · 2026Article
- Mitochondrial dysfunction in neurodegenerative disorders: mechanisms and therapeutic advances.Molecular biomedicine · 2026Review
- Nanotube-Assisted Motor Neuron and Neuromuscular Junction Stabilization in Spinal Muscular Atrophy: A Hypothesis for Adjunctive Therapy.Neurology international · 2026Review
- Upregulation of sphingomyelin and ABCA8 in response to TDP-43 pathology in amyotrophic lateral sclerosis brain.Brain pathology (Zurich, Switzerland) · 2026Article
- TDP-43 impairs glycolysis by sequestering hexokinase 1 in amyotrophic lateral sclerosis.Acta neuropathologica · 2026Article
- Anatomical Associations Between Focal Mitochondrial Metabolism and Patterns of Neurodegeneration in Amyotrophic Lateral Sclerosis.Annals of neurology · 2026Article
- From autophagy-lysosomal deficits to neurodegeneration in Niemann-Pick type C1 disease: implications for age-related neurodegenerative disorders.Frontiers in neuroscience · 2026Review
- Defining spinal motor neuron subtypes across development: from embryonic specification to postnatal maturation.Frontiers in cellular neuroscience · 2026Review
- Axonal transport impairment as an upstream mechanism in amyotrophic lateral sclerosis pathogenesis.Frontiers in neuroscience · 2026Article
- Astrocytic KFrontiers in aging neuroscience · 2026Review
- Extracellular RNAs as Messengers and Early Biomarkers in Neurodegeneration.International journal of molecular sciences · 2025Review
- PPA1 Facilitates Thermogenesis in Brown and Beige Fat by Regulating the Mitochondrial Localization of FUS.Current medical science · 2025Article
- [Heterogeneity in the regulation of cellular stress responses byZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Article
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Authors and funding
14 authors.
Funding
Abstract
Mutations in FUS and TARDBP cause amyotrophic lateral sclerosis (ALS), but the precise mechanisms of selective motor neuron degeneration remain unresolved. To address if pathomechanisms are shared across mutations and related to either gain- or loss-of-function, we performed single-cell RNA sequencing across isogenic induced pluripotent stem cell-derived neuron types, harbouring FUS P525L, FUS R495X, TARDBP M337V mutations or FUS knockout. Transcriptional changes were far more pronounced in motor neurons than interneurons. About 20% of uniquely dysregulated motor neuron transcripts were shared across FUS mutations, half from gain-of-function. Most indicated mitochondrial impairments, with attenuated pathways shared with mutant TARDBP M337V as well as C9orf72-ALS patient motor neurons. Mitochondrial motility was impaired in ALS motor axons, even with nuclear localized FUS mutants, demonstrating shared toxic gain-of-function mechanisms across FUS- and TARDBP-ALS, uncoupled from protein mislocalization. These early mitochondrial dysfunctions unique to motor neurons may affect survival and represent therapeutic targets in ALS.
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