Robust Neuritogenesis-Promoting Activity by Bis(heptyl)-Cognitin Through the Activation of alpha7-Nicotinic Acetylcholine Receptor/ERK Pathway

Sheng Quan Hu, Wei Cui, Shing Hung Mak, Chung Lit Choi, Yuan Jia Hu, Gang Li, Karl Wah Keung Tsim, Yuan-Ping Pang, Yi Fan Han

Research output: Contribution to journalArticle

6 Scopus citations

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 languageEnglish (US)
Pages (from-to)520-529
Number of pages10
JournalCNS Neuroscience and Therapeutics
Volume21
Issue number6
DOIs
StatePublished - Jun 1 2015

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Keywords

  • Alpha7-nicotinic acetylcholine receptor
  • Bis(heptyl)-cognitin
  • Extracellular signal-regulated kinase
  • Neurite outgrowth
  • Neurodegenerative disorders

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Physiology (medical)
  • Psychiatry and Mental health
  • Pharmacology

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