ArticleCells2022
Neurotoxic Astrocytes Directly Converted from Sporadic and Familial ALS Patient Fibroblasts Reveal Signature Diversities and miR-146a Theragnostic Potential in Specific Subtypes.
Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- A molecular systems architecture of neuromuscular junction in amyotrophic lateral sclerosis.NPJ systems biology and applications · 2025Pooled it
- Neuromodulatory role and therapeutic potential of N 6 -methyladenosine RNA methylation in neurodegenerative diseases.Neural regeneration research · 2026Article
- Extracellular vesicle-derived MicroRNAs as potential therapies for spinal cord and peripheral nerve injuries.RNA biology · 2025Review
- Inorganic Polyphosphate: An Emerging Regulator of Neuronal Bioenergetics and Its Implications in Neuroprotection.Biomolecules · 2025Review
- Glioinflammation: disease-associated microglia and astrocytes in psychiatric disorders, neurodegeneration, and senescence.Frontiers in cellular neuroscience · 2025Review
- Pathogenic synergy: dysfunctional mitochondria and neuroinflammation in neurodegenerative diseases associated with aging.Frontiers in aging · 2025Review
- Article
- Optineurin overexpression ameliorates neurodegeneration through regulating neuroinflammation and mitochondrial quality in a murine model of amyotrophic lateral sclerosis.Frontiers in aging neuroscience · 2025Article
- Astrocytes Lingering at a Crossroads: Neuroprotection and Neurodegeneration in Neurocognitive Dysfunction.International journal of biological sciences · 2025Review
- Shared and distinct changes in the molecular cargo of extracellular vesicles in different neurodegenerative diseases.Cellular and molecular life sciences : CMLS · 2024Review
- Induction of astrocyte reactivity promotes neurodegeneration in human pluripotent stem cell models.Stem cell reports · 2024Article
- Astrocytes: The Stars in Neurodegeneration?Biomolecules · 2024Review
- The Essential Role of Astrocytes in Neurodegeneration and Neuroprotection.CNS & neurological disorders drug targets · 2024Review
- MicroRNA biomarkers as next-generation diagnostic tools for neurodegenerative diseases: a comprehensive review.Frontiers in molecular neuroscience · 2024Review
- Revisiting the critical roles of reactive astrocytes in neurodegeneration.Molecular psychiatry · 2023Review
- Astrocytes: Dissecting Their Diverse Roles in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.Cells · 2023Review
- MiR-146a in ALS: Contribution to Early Peripheral Nerve Degeneration and Relevance as Disease Biomarker.International journal of molecular sciences · 2023Article
- Why should we care about astrocytes in a motor neuron disease?Frontiers in molecular medicine · 2023Review
- Mature iPSC-derived astrocytes of an ALS/FTD patient carrying the TDP43Frontiers in cell and developmental biology · 2023Article
- Remodeling of astrocyte secretome in amyotrophic lateral sclerosis: uncovering novel targets to combat astrocyte-mediated toxicity.Translational neurodegeneration · 2022Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
A lack of stratification methods in patients with amyotrophic lateral sclerosis (ALS) is likely implicated in therapeutic failures. Regional diversities and pathophysiological abnormalities in astrocytes from mice with SOD1 mutations (mSOD1-ALS) can now be explored in human patients using somatic cell reprogramming. Here, fibroblasts from four sporadic (sALS) and three mSOD1-ALS patients were transdifferentiated into induced astrocytes (iAstrocytes). ALS iAstrocytes were neurotoxic toward HB9-GFP mouse motor neurons (MNs) and exhibited subtype stratification through GFAP, CX43, Ki-67, miR-155 and miR-146a expression levels. Up- (two cases) and down-regulated (three cases) miR-146a values in iAstrocytes were recapitulated in their secretome, either free or as cargo in small extracellular vesicles (sEVs). We previously showed that the neuroprotective phenotype of depleted miR-146 mSOD1 cortical astrocytes was reverted by its mimic. Thus, we tested such modulation in the most miR-146a-depleted patient-iAstrocytes (one sALS and one mSOD1-ALS). The miR-146a mimic in ALS iAstrocytes counteracted their reactive/inflammatory profile and restored miR-146a levels in sEVs. A reduction in lysosomal activity and enhanced synaptic/axonal transport-related genes in NSC-34 MNs occurred after co-culture with miR-146a-modulated iAstrocytes. In summary, the regulation of miR-146a in depleted ALS astrocytes may be key in reestablishing their normal function and in restoring MN lysosomal/synaptic dynamic plasticity in disease sub-groups.
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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.