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Histone Deacetylase Inhibition Activity and Molecular Docking of ( E )‐Resveratrol: Its Therapeutic Potential in Spinal Muscular Atrophy
Author(s) -
DayangaçErden Didem,
Bora Gamze,
Ayhan Peruze,
Kocaefe Çetin,
Dalkara Sevim,
Yelekçi Kemal,
Demir Ayhan S.,
ErdemYurter Hayat
Publication year - 2009
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2009.00781.x
Subject(s) - resveratrol , spinal muscular atrophy , smn1 , histone deacetylase , histone deacetylase inhibitor , motor neuron , chemistry , pharmacology , histone , biology , microbiology and biotechnology , cancer research , biochemistry , spinal cord , gene , neuroscience
Spinal muscular atrophy is an autosomal recessive motor neuron disease that is caused by mutation of the survival motor neuron gene ( SMN1 ) but all patients retain a nearly identical copy, SMN2 . The disease severity correlates inversely with increased SMN2 copy. Currently, the most promising therapeutic strategy for spinal muscular atrophy is induction of SMN2 gene expression by histone deacetylase inhibitors. Polyphenols are known for protection against oxidative stress and degenerative diseases. Among our candidate prodrug library, we found that ( E )‐resveratrol, which is one of the polyphenolic compounds, inhibited histone deacetylase activity in a concentration‐dependent manner and half‐maximum inhibition was observed at 650 μ m . Molecular docking studies showed that ( E )‐resveratrol had more favorable free energy of binding (−9.09 kcal/mol) and inhibition constant values (0.219 μ m ) than known inhibitors. To evaluate the effect of ( E )‐resveratrol on SMN2 expression, spinal muscular atrophy type I fibroblast cell lines was treated with ( E )‐resveratrol. The level of full‐length SMN2 mRNA and protein showed 1.2‐ to 1.3‐fold increase after treatment with 100 μ m ( E )‐resveratrol in only one cell line. These results indicate that response to ( E )‐resveratrol treatment is variable among cell lines. This data demonstrate a novel activity of ( E )‐resveratrol and that it could be a promising candidate for the treatment of spinal muscular atrophy.