Abstract
Aims: Neurodegenerative disorders are caused by progressive neuronal loss in the brain, and hence, compounds that could promote neuritogenesis may have therapeutic values. In this study, the effects of bis(heptyl)-cognitin (B7C), a multifunctional dimer, on neurite outgrowth were investigated in both PC12 cells and primary cortical neurons. Methods: Immunocytochemical staining was used to evaluate the proneuritogenesis effects, and Western blot and short hairpin RNA assays were applied to explore the underlying mechanisms. Results: B7C (0.1-0.5 μM) induced robust neurite outgrowth in PC12 cells, as evidenced by the neurite-bearing morphology and upregulation of growth-associated protein-43 expression. In addition, B7C markedly promoted neurite outgrowth in primary cortical neurons as shown by the increase in the length of β-III-tubulin-positive neurites. Furthermore, B7C rapidly increased ERK phosphorylation. Specific inhibitors of alpha7-nicotinic acetylcholine receptor (α7-nAChR) and MEK, but not those of p38 or JNK, blocked the neurite outgrowth as well as ERK phosphorylation induced by B7C. Most importantly, genetic depletion of α7-nAChR significantly abolished B7C-induced neurite outgrowth in PC12 cells. Conclusion: B7C promoted neurite outgrowth through the activation of α7-nAChR/ERK pathway, which offers novel insight into the potential application of B7C in the treatment of neurodegenerative disorders.
Original language | English |
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Pages (from-to) | 520-529 |
Number of pages | 10 |
Journal | CNS Neuroscience and Therapeutics |
Volume | 21 |
Issue number | 6 |
DOIs | |
Publication status | Published - 1 Jun 2015 |
Keywords
- Alpha7-nicotinic acetylcholine receptor
- Bis(heptyl)-cognitin
- Extracellular signal-regulated kinase
- Neurite outgrowth
- Neurodegenerative disorders
ASJC Scopus subject areas
- Pharmacology
- Psychiatry and Mental health
- Physiology (medical)
- Pharmacology (medical)