HDAC inhibitors induce BDNF expression and promote neurite outgrowth in human neural progenitor cells-derived neurons

Amir Bagheri, Parham Habibzadeh, Seyedeh Fatemeh Razavipour, Claude Henry Volmar, Nancy T. Chee, Shaun P. Brothers, Claes Wahlestedt, Seyed Javad Mowla, Mohammad Ali Faghihi

Research output: Contribution to journalArticle

2 Scopus citations

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 languageEnglish (US)
Article number1109
JournalInternational journal of molecular sciences
Volume20
Issue number5
DOIs
StatePublished - Mar 2019

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

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