Abstract
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.
| Original language | English (US) |
|---|---|
| Journal | International journal of molecular sciences |
| Volume | 20 |
| Issue number | 5 |
| DOIs | |
| State | Published - Mar 5 2019 |
Fingerprint
Keywords
- BDNF
- epigenetic library
- HDAC inhibitor
- human neural progenitor cell
- neurite outgrowth
- neurodegenerative disorder
- screening
ASJC Scopus subject areas
- Catalysis
- Molecular Biology
- Spectroscopy
- Computer Science Applications
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry
Cite this
HDAC Inhibitors Induce BDNF Expression and Promote Neurite Outgrowth in Human Neural Progenitor Cells-Derived Neurons. / Bagheri, Amir; Habibzadeh, Parham; Razavipour, Seyedeh Fatemeh; Volmar, Claude Henry; Chee, Nancy T.; Brothers, Shaun P; Wahlestedt, Claes R; Mowla, Seyed Javad; Faghihi, Mohammad A.
In: International journal of molecular sciences, Vol. 20, No. 5, 05.03.2019.Research output: Contribution to journal › Article
}
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 R
AU - Mowla, Seyed Javad
AU - Faghihi, Mohammad A
PY - 2019/3/5
Y1 - 2019/3/5
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
UR - http://www.scopus.com/inward/record.url?scp=85062629557&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062629557&partnerID=8YFLogxK
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
ER -