ArticleScientific reports2018
Small-molecule flunarizine increases SMN protein in nuclear Cajal bodies and motor function in a mouse model of spinal muscular atrophy.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 12 citations in OpenAlex.
- Multi-omics analysis reveals the effects of Codonopsis pilosula polysaccharides on the skeletal muscle development of Sansui ducks during the embryonic stage.Poultry science · 2026Article
- Flunarizine changes microRNA expression in cell cultures and in a mouse model of spinal muscular atrophy.Scientific reports · 2026Article
- The effect of coadministration of D156844 and AR42 (REC-2282) on the survival and motor phenotype of mice with spinal muscular atrophy.Scientific reports · 2025Article
- Understanding the Role of the SMN Complex Component GEMIN5 and Its Functional Relationship with Demethylase KDM6B in the Flunarizine-Mediated Neuroprotection of Motor Neuron Disease Spinal Muscular Atrophy.International journal of molecular sciences · 2024Article
- Evaluation of the orally bioavailable 4-phenylbutyrate-tethered trichostatin A analogue AR42 in models of spinal muscular atrophy.Scientific reports · 2023Article
- NADPH oxidase 4 inhibition is a complementary therapeutic strategy for spinal muscular atrophy.Frontiers in cellular neuroscience · 2023Article
- A link between agrin signalling and CaScientific reports · 2022Article
- Spinal muscular atrophy: From approved therapies to future therapeutic targets for personalized medicine.Cell reports. Medicine · 2021Review
- Anti-prion Drugs Targeting the Protein Folding Activity of the Ribosome Reduce PABPN1 Aggregation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- The Small-Molecule Flunarizine in Spinal Muscular Atrophy Patient Fibroblasts Impacts on the Gemin Components of the SMN Complex and TDP43, an RNA-Binding Protein Relevant to Motor Neuron Diseases.Frontiers in molecular biosciences · 2020Article
- Disruption of RNA Metabolism in Neurological Diseases and Emerging Therapeutic Interventions.Neuron · 2019Review
- Accumulation of poly(A) RNA in nuclear granules enriched in Sam68 in motor neurons from the SMNΔ7 mouse model of SMA.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
The hereditary neurodegenerative disorder spinal muscular atrophy (SMA) is characterized by the loss of spinal cord motor neurons and skeletal muscle atrophy. SMA is caused by mutations of the survival motor neuron (SMN) gene leading to a decrease in SMN protein levels. The SMN deficiency alters nuclear body formation and whether it can contribute to the disease remains unclear. Here we screen a series of small-molecules on SMA patient fibroblasts and identify flunarizine that accumulates SMN into Cajal bodies, the nuclear bodies important for the spliceosomal small nuclear RNA (snRNA)-ribonucleoprotein biogenesis. Using histochemistry, real-time RT-PCR and behavioural analyses in a mouse model of SMA, we show that along with the accumulation of SMN into Cajal bodies of spinal cord motor neurons, flunarizine treatment modulates the relative abundance of specific spliceosomal snRNAs in a tissue-dependent manner and can improve the synaptic connections and survival of spinal cord motor neurons. The treatment also protects skeletal muscles from cell death and atrophy, raises the neuromuscular junction maturation and prolongs life span by as much as 40 percent (p < 0.001). Our findings provide a functional link between flunarizine and SMA pathology, highlighting the potential benefits of flunarizine in a novel therapeutic perspective against neurodegenerative diseases.
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