Carboxylic acid derivatives of histone deacetylase inhibitors induce full length SMN2 transcripts: a promising target for spinal muscular atrophy therapeutics.
Introduction: 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...
| Publicado en: | Archives of Medical Science Vol. 7; no. 2; pp. 230 - 235 |
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| Autores principales: | , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Termedia Publishing House
2011 Apr
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=108224861&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 108224861 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 17341922 77TB jtl: Archives of Medical Science issn: 17341922 maglogo: N pubinfo: dt: 2011 Apr vid: 7 iid: 2 pid: 24295 pub: Termedia Publishing House place: , <Blank> artinfo: ui: 108224861 108224861 NLM22291761 2011343677 10.5114/aoms.2011.22072 NLM22291761 PMC3258711 108224861 ppf: 230 ppct: 5 formats: tig: atl: Carboxylic acid derivatives of histone deacetylase inhibitors induce full length SMN2 transcripts: a promising target for spinal muscular atrophy therapeutics. aug: au: Dayangac-Erden, Didem Bora-Tatar, Gamze Dalkara, Sevim Demir, Ayhan S. Erdem-Yurter, Hayat affil: Department of Medical Biology, Faculty of Medicine, Hacettepe University, Ankara, Turkey sug: subj: Carboxylic Acids Therapeutic Use Genomics Muscular Atrophy Familial and Genetic Muscular Atrophy Prevention and Control Blotting, Western Equipment and Supplies Funding Source Human In Vitro Studies Reverse Transcriptase Polymerase Chain Reaction Turkiye ab: Introduction: 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.Material and Methods: 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.Results: 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.Conclusions: Our data suggest that carboxylic acid derivatives including phenolic structure and symmetry could be a good candidate for SMA treatment. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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