Carboxylic acid derivatives of histone deacetylase inhibitors induce full length SMN2 transcripts: a promising target for spinal muscular atrophy therapeutics

Download

10.5114:aoms.2011.22072.pdf

Date

2011-4

Author

Dayangac Erden, Didem
Bora Tatar, Gamze
Dalkara, Sevim
Demir, Ayhan S.
Erdem Yurter, Hayat

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

137
views

78
downloads

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.

Subject Keywords

Histone deacetylase inhibitors, SMN2 gene, Therapy

URI

https://hdl.handle.net/11511/50938

Journal

Archives of Medical Science

DOI

https://doi.org/10.5114/aoms.2011.22072

Collections

Department of Chemistry, Article

Suggestions

OpenMETU
Core

Histone Deacetylase Inhibition Activity and Molecular Docking of (E )-Resveratrol: Its Therapeutic Potential in Spinal Muscular Atrophy DAYANGAÇ ERDEN, DİDEM; BORA, GAMZE; Ayhan, Peruze; Kocaefe, Cetin; DALKARA, SEVİM; YELEKÇİ, Kemal; Demir, Ayhan Sıtkı; Erdem-Yurter, Hayat (2009-03-01) 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 ...
Intelligent Ratio: A New Method for Carrier and Newborn Screening in Spinal Muscular Atrophy Cavdarli, Busranur; Ozturk, Fatma Nihal; Guntekin Ergun, Sezen; ERGÜN, MEHMET ALİ; Dogan, Ozlem; Percin, Emriye Ferda (Mary Ann Liebert Inc, 2020-09-01) Aim:Spinal muscular atrophy (SMA) is an inherited, autosomal recessive neuromuscular disease that causes high morbidity and mortality. The prevalence is 1-2/100,000, while the incidence is 1/6000-1/10,000 among live births. Due to the high carrier frequency (1/40-1/60) of SMA, screening can prevent new cases. The aim of the current study was to present the development of a new, quantitative, real-time, polymerase chain reaction (PCR)-based screening test that uses an intelligent ratio (IR) for analyses, as ...
SMN loss dysregulates microtubule-associated proteins in spinal muscular atrophy model Zobaroğlu Özer, Pelin; Koyunoğlu, Dila; Son, Çağdaş Devrim; Erdem-Yurter, Hayat Erdem; BORA, GAMZE (2022-05-01) © 2022 Elsevier Inc.Spinal muscular atrophy (SMA) is a rare neurodegenerative disease caused by the absence of survival motor neuron (SMN) protein. SMN loss results in impairments of the cytoskeleton, including microtubules and regulatory proteins. However, the contribution of microtubule-associated proteins (MAPs) to microtubule dysregulations in SMA is not fully understood. In this study, we investigated neuronal MAPs responsible for the microtubule stability and growth, including MAP1A, MAP2, MAP6, MAP7,...
Mutation in MEOX1 gene causes a recessive Klippel-Feil syndrome subtype Bayrakli, Fatih; Guclu, Bulent; Yakicier, Cengiz; Balaban, Hatice; Kartal, Ugur; Erguner, Bekir; Sagiroglu, Mahmut; Yuksel, Sirin; Ozturk, Ahmet; Kazanci, Burak; Ozum, Unal; Kars, Hamit (Springer Science and Business Media LLC, 2013) Background: Klippel-Feil syndrome (KFS) is characterized by the developmental failure of the cervical spine and has two dominantly inherited subtypes. Affected individuals who are the children of a consanguineous marriage are extremely rare in the medical literature, but the gene responsible for this recessive trait subtype of KFS has recently been reported. Results: We identified a family with the KFS phenotype in which their parents have a consanguineous marriage. Radiological examinations revealed tha...
End-binding 3 protein alterations in an in vitro spinal muscular atrophy model Koyunoğlu, Dila; Bora, Gamze; Son, Çağdaş Devrim; Yurter, Hayat (2019-09-27) Background/aim:Spinal muscular atrophy (SMA) is a rare neurodegenerative disease which is caused by mutations in Survival of motor neuron 1(SMN1) gene. Absence of SMN protein leads to cytoskeleton defects, especially in neurons, due to dysregulations in regulatory proteins. Our previous results showed impaired microtubule stability in SMN depleted cells and also alterations in some microtubule associated proteins, including microtubule-associated protein 1B (MAP1B). MAP...

Citation Formats

D. Dayangac Erden, G. Bora Tatar, S. Dalkara, A. S. Demir, and H. Erdem Yurter, “Carboxylic acid derivatives of histone deacetylase inhibitors induce full length SMN2 transcripts: a promising target for spinal muscular atrophy therapeutics,” Archives of Medical Science, pp. 230–234, 2011, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/50938.