TY - JOUR
T1 - HDAC inhibitors induce BDNF expression and promote neurite outgrowth in human neural progenitor cells-derived neurons
AU - Bagheri, Amir
AU - Habibzadeh, Parham
AU - Razavipour, Seyedeh Fatemeh
AU - Volmar, Claude Henry
AU - Chee, Nancy T.
AU - Brothers, Shaun P.
AU - Wahlestedt, Claes
AU - Mowla, Seyed Javad
AU - Faghihi, Mohammad Ali
N1 - Funding Information:
This research was funded by US NIH NINDS R01NS081208-01A1 and NIMAD research grant (940714) awarded to MAF. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
Funding Information:
Funding: This research was funded by US NIH NINDS R01NS081208-01A1 and NIMAD research grant (940714) awarded to MAF. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/3
Y1 - 2019/3
N2 - 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.
AB - 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.
KW - BDNF
KW - Epigenetic library
KW - HDAC inhibitor
KW - Human neural progenitor cell
KW - Neurite outgrowth
KW - Neurodegenerative disorder
KW - Screening
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U2 - 10.3390/ijms20051109
DO - 10.3390/ijms20051109
M3 - Article
C2 - 30841499
AN - SCOPUS:85062629557
VL - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 5
M1 - 1109
ER -