HDAC Inhibitors Induce BDNF Expression and Promote Neurite Outgrowth in Human Neural Progenitor Cells-Derived Neurons.
Amir BagheriParham HabibzadehSeyedeh Fatemeh RazavipourClaude-Henry VolmarNancy T CheeShaun P BrothersClaes WahlestedtSeyed Javad MowlaMohammad Ali FaghihiPublished in: International journal of molecular sciences (2019)
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.
Keyphrases
- histone deacetylase
- poor prognosis
- stress induced
- endothelial cells
- spinal cord injury
- spinal cord
- high throughput
- gene expression
- acute coronary syndrome
- signaling pathway
- heart failure
- induced apoptosis
- coronary artery disease
- cerebral ischemia
- stem cells
- cell proliferation
- dna methylation
- mesenchymal stem cells
- cell therapy
- oxidative stress
- antiplatelet therapy
- left ventricular
- magnetic resonance
- neural stem cells
- endoplasmic reticulum stress