HDAC Inhibitors Induce
| Autor: | Amir, Bagheri, Parham, Habibzadeh, Seyedeh Fatemeh, Razavipour, Claude-Henry, Volmar, Nancy T, Chee, Shaun P, Brothers, Claes, Wahlestedt, Seyed Javad, Mowla, Mohammad Ali, Faghihi |
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| Rok vydání: | 2019 |
| Předmět: |
epigenetic library
neurite outgrowth human neural progenitor cell Brain-Derived Neurotrophic Factor screening Neuronal Outgrowth Hydroxamic Acids Article Histone Deacetylase Inhibitors HEK293 Cells BDNF nervous system Neural Stem Cells HDAC inhibitor Humans Benzimidazoles neurodegenerative disorder Cells Cultured Benzofurans |
| Zdroj: | International Journal of Molecular Sciences |
| ISSN: | 1422-0067 |
| Popis: | Besides its key role in neural development, brain-derived neurotrophic factor (BDNF) is important for long-term potentiation and neurogenesis, which makes it a critical factor in learning and memory. Due to the important role of BDNF in synaptic function and plasticity, an in-house epigenetic library was screened against human neural progenitor cells (HNPCs) and WS1 human skin fibroblast cells using Cell-to-Ct assay kit to identify the small compounds capable of modulating the BDNF expression. In addition to two well-known hydroxamic acid-based histone deacetylase inhibitors (hb-HDACis), SAHA and TSA, several structurally similar HDAC inhibitors including SB-939, PCI-24781 and JNJ-26481585 with even higher impact on BDNF expression, were discovered in this study. Furthermore, by using well-developed immunohistochemistry assays, the selected compounds were also proved to have neurogenic potential improving the neurite outgrowth in HNPCs-derived neurons. In conclusion, we proved the neurogenic potential of several hb-HDACis, alongside their ability to enhance BDNF expression, which by modulating the neurogenesis and/or compensating for neuronal loss, could be propitious for treatment of neurological disorders. |
| Databáze: | OpenAIRE |
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