ArticleJournal of neuroinflammation2021
Targeting S100A4 with niclosamide attenuates inflammatory and profibrotic pathways in models of amyotrophic lateral sclerosis.
Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- Inactivation of SERCA2 at Cys674 induces skeletal muscle atrophy by activating the TGFβ/Smad-S100a4 axis to promote inflammation.Redox biology · 2026Article
- Therapeutic Effect of Niclosamide versus Triamcinolone on Rabbit Ear Model of Hypertrophic Scar.Aesthetic plastic surgery · 2026Article
- S100A4 enhances the pro-fibrotic effect of macrophage to promote collagen capsule formation of Trichinella spiralis.PLoS neglected tropical diseases · 2026Article
- S100A4 Orchestrates Fibroblast Fate to Drive Fibrotic Remodeling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Repurposing niclosamide to mitigate inflammaging: a review of multi-target mechanisms in cellular senescence and age-related decline.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Severe fever with thrombocytopenia syndrome virus infection of the male reproductive tract induces pathology and inflammation.Nature microbiology · 2026Article
- S100A4 triggeres the pyroptosis of vsmcs: association with mitochondrial damage, impaired mitophagy, and CaBiology direct · 2026Article
- Inhibition of S100A4 decreases neurotoxic astrocyte reactivity and attenuates neuropathic pain via the TLR4/NF-κB pathway in a rat model of spinal nerve ligation.The journal of headache and pain · 2025Article
- The multi-faceted immune modulatory role of S100A4 in cancer and chronic inflammatory disease.Frontiers in immunology · 2025Review
- Article
- Natural Products from Chinese Medicine Targeting NF-κB Signaling: Emerging Therapeutic Avenues for Neurodegenerative Diseases.Drug design, development and therapy · 2025Review
- Review
- Endogenous retroviruses are dysregulated in ALS.iScience · 2024Article
- Unveiling the fibrotic puzzle of endometriosis: An overlooked concern calling for prompt action.F1000Research · 2024Review
- Repurposing niclosamide for the treatment of neurological disorders.Neural regeneration research · 2023Article
- Article
- Article
- Niclosamide Attenuates Inflammation-Associated Profibrotic Responses in Human Subepithelial Lung Myofibroblasts.Biomedicines · 2023Article
- Integrating Comorbidity Knowledge for Alzheimer's Disease Drug Repurposing using Multi-task Graph Neural Network.AMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science · 2023Article
- Metformin attenuates fibroblast activation during pulmonary fibrosis by targeting S100A4Frontiers in pharmacology · 2023Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAn increasing number of studies evidences that amyotrophic lateral sclerosis (ALS) is characterized by extensive alterations in different cell types and in different regions besides the CNS. We previously reported the upregulation in ALS models of a gene called fibroblast-specific protein-1 or S100A4, recognized as a pro-inflammatory and profibrotic factor. Since inflammation and fibrosis are often mutual-sustaining events that contribute to establish a hostile environment for organ functions, the comprehension of the elements responsible for these interconnected pathways is crucial to disclose novel aspects involved in ALS pathology.
methodsHere, we employed fibroblasts derived from ALS patients harboring the C9orf72 hexanucleotide repeat expansion and ALS patients with no mutations in known ALS-associated genes and we downregulated S100A4 using siRNA or the S100A4 transcriptional inhibitor niclosamide. Mice overexpressing human FUS were adopted to assess the effects of niclosamide in vivo on ALS pathology.
resultsWe demonstrated that S100A4 underlies impaired autophagy and a profibrotic phenotype, which characterize ALS fibroblasts. Indeed, its inhibition reduces inflammatory, autophagic, and profibrotic pathways in ALS fibroblasts, and interferes with different markers known as pathogenic in the disease, such as mTOR, SQSTM1/p62, STAT3, α-SMA, and NF-κB. Importantly, niclosamide in vivo treatment of ALS-FUS mice reduces the expression of S100A4, α-SMA, and PDGFRβ in the spinal cord, as well as gliosis in central and peripheral nervous tissues, together with axonal impairment and displays beneficial effects on muscle atrophy, by promoting muscle regeneration and reducing fibrosis.
conclusionOur findings show that S100A4 has a role in ALS-related mechanisms, and that drugs such as niclosamide which are able to target inflammatory and fibrotic pathways could represent promising pharmacological tools for ALS.
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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.