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• W2043614399 abstract "Proximal spinal muscular atrophy (SMA) is a common autosomal recessively inherited neuromuscular disorder. It is caused by homozygous absence of the survival motor neuron 1 (SMN1) gene. SMN2, which modulates the severity of the disease, represents a major target for therapy. The aim of this study was to investigate whether SMN2 expression can be increased by caffeic acid, chlorogenic acid and curcumin, which are designed by modifications of the carboxylic acid class of histone deacetylase (HDAC) inhibitors.Using quantitative real-time PCR, we analysed the levels of full-length SMN2 and Δ7SMN2 mRNA. We performed LDH cytotoxicity assay to analyse whether SMN2 activating concentrations of caffeic acid, chlorogenic acid and curcumin were cytotoxic to fibroblasts.We found that caffeic acid and curcumin were more efficient than chlorogenic acid and increased full-length SMN2 mRNA levels 1.5 and 1.7-fold, respectively. Δ7SMN2 mRNA levels were measured to investigate alternative splicing of exon 7. We also found that cytotoxicity was not observed at SMN2 activating concentrations.Our data suggest that carboxylic acid derivatives including phenolic structure and symmetry could be a good candidate for SMA treatment." @default.
• W2043614399 created "2016-06-24" @default.
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• W2043614399 date "2011-01-01" @default.
• W2043614399 modified "2023-10-18" @default.
• W2043614399 title "Carboxylic acid derivatives of histone deacetylase inhibitors induce full length SMN2 transcripts: a promising target for spinal muscular atrophy therapeutics" @default.
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• W2043614399 doi "https://doi.org/10.5114/aoms.2011.22072" @default.
• W2043614399 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3258711" @default.
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