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Carboxylic acid derivatives of histone deacetylase inhibitors induce full length SMN2 transcripts: a promising target for spinal muscular atrophy therapeutics.
MedLine Citation:
PMID:  22291761     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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.
Authors:
Didem Dayangac-Erden; Gamze Bora-Tatar; Sevim Dalkara; Ayhan S Demir; Hayat Erdem-Yurter
Publication Detail:
Type:  Journal Article     Date:  2011-05-17
Journal Detail:
Title:  Archives of medical science : AMS     Volume:  7     ISSN:  1896-9151     ISO Abbreviation:  Arch Med Sci     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2012-01-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101258257     Medline TA:  Arch Med Sci     Country:  Poland    
Other Details:
Languages:  eng     Pagination:  230-4     Citation Subset:  -    
Affiliation:
Department of Medical Biology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
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