ArticleJournal of neurology2020
ALS-derived fibroblasts exhibit reduced proliferation rate, cytoplasmic TDP-43 aggregation and a higher susceptibility to DNA damage.
Article in Journal of neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- 3D Artificial Skin Model As a Novel Strategy for the Detection of Pyroptosis-Cascade Activation in Amyotrophic Lateral Sclerosis.ACS applied materials & interfaces · 2026Article
- A Family with Meester-Loeys Syndrome Caused by a Novel Missense Variant in theInternational journal of molecular sciences · 2025Article
- A cellular model of TDP-43 induces phosphorylated TDP-43 aggregation with distinct changes in solubility and autophagy dysregulation.The FEBS journal · 2025Article
- Skin pathology in ALS: Diagnostic implications and biomarker potential.Biomolecules & biomedicine · 2025Review
- TDP-43-proteinopathy at the crossroads of tauopathy: on copathology and current and prospective biomarkers.Frontiers in cellular neuroscience · 2025Review
- Experimental Cell Models for Investigating Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- In vivo diagnosis of TDP-43 proteinopathies: in search of biomarkers of clinical use.Translational neurodegeneration · 2024Review
- Review
- The new missense G376V-TDP-43 variant induces late-onset distal myopathy but not amyotrophic lateral sclerosis.Brain : a journal of neurology · 2024Article
- Protein aggregation and therapeutic strategies in SOD1- and TDP-43- linked ALS.Frontiers in molecular biosciences · 2024Review
- Characteristics of Sensory Neuron Dysfunction in Amyotrophic Lateral Sclerosis (ALS): Potential for ALS Therapy.Biomedicines · 2023Review
- Review
- Effects of PB-TURSO on the transcriptional and metabolic landscape of sporadic ALS fibroblasts.Annals of clinical and translational neurology · 2022Article
- ALS monocyte-derived microglia-like cells reveal cytoplasmic TDP-43 accumulation, DNA damage, and cell-specific impairment of phagocytosis associated with disease progression.Journal of neuroinflammation · 2022Article
- Article
- Article
- DNA Damage, Defective DNA Repair, and Neurodegeneration in Amyotrophic Lateral Sclerosis.Frontiers in aging neuroscience · 2022Review
- DNA damage as a mechanism of neurodegeneration in ALS and a contributor to astrocyte toxicity.Cellular and molecular life sciences : CMLS · 2021Review
- Targeting S100A4 with niclosamide attenuates inflammatory and profibrotic pathways in models of amyotrophic lateral sclerosis.Journal of neuroinflammation · 2021Article
- TDP-43 Vasculopathy in the Spinal Cord in Sporadic Amyotrophic Lateral Sclerosis (sALS) and Frontal Cortex in sALS/FTLD-TDP.Journal of neuropathology and experimental neurology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundDermic fibroblasts have been proposed as a potential genetic-ALS cellular model. This study aimed to explore whether dermic fibroblasts from patients with sporadic-ALS (sALS) recapitulate alterations typical of ALS motor neurons and exhibit abnormal DNA-damage response.
methodsDermic fibroblasts were obtained from eight sALS patients and four control subjects. Cellular characterization included proliferation rate analysis, cytoarchitecture studies and confocal immunofluorescence assessment for TDP-43. Additionally, basal and irradiation-induced DNA damage was evaluated by confocal immunofluorescence and biochemical techniques.
resultssALS-fibroblasts showed decreased proliferation rates compared to controls. Additionally, whereas control fibroblasts exhibited the expected normal spindle-shaped morphology, ALS fibroblasts were thinner, with reduced cell size and enlarged nucleoli, with frequent cytoplasmic TDP-43aggregates. Also, baseline signs of DNA damage were evidenced more frequently in ALS-derived fibroblasts (11 versus 4% in control-fibroblasts). Assays for evaluating the irradiation-induced DNA damage demonstrated that DNA repair was defective in ALS-fibroblasts, accumulating more than double of γH2AX-positive DNA damage foci than controls. Very intriguingly, the proportion of fibroblasts particularly vulnerable to irradiation (with more than 15 DNA damage foci per nucleus) was seven times higher in ALS-derived fibroblasts than in controls.
conclusionsDermic-derived ALS fibroblasts recapitulate relevant cellular features of sALS and show a higher susceptibility to DNA damage and defective DNA repair responses. Altogether, these results support that dermic fibroblasts may represent a convenient and accessible ALS cellular model to study pathogenetic mechanisms, particularly those related to DNA damage response, as well as the eventual response to disease-modifying therapies.
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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.