TY - JOUR
T1 - Robust Neuritogenesis-Promoting Activity by Bis(heptyl)-Cognitin Through the Activation of alpha7-Nicotinic Acetylcholine Receptor/ERK Pathway
AU - Hu, Sheng Quan
AU - Cui, Wei
AU - Mak, Shing Hung
AU - Choi, Chung Lit
AU - Hu, Yuan Jia
AU - Li, Gang
AU - Tsim, Karl Wah Keung
AU - Pang, Yuan Ping
AU - Han, Yi Fan
N1 - Publisher Copyright:
© 2015 John Wiley & Sons Ltd.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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.
AB - 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.
KW - Alpha7-nicotinic acetylcholine receptor
KW - Bis(heptyl)-cognitin
KW - Extracellular signal-regulated kinase
KW - Neurite outgrowth
KW - Neurodegenerative disorders
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U2 - 10.1111/cns.12401
DO - 10.1111/cns.12401
M3 - Article
C2 - 25917415
AN - SCOPUS:84929518982
SN - 1755-5930
VL - 21
SP - 520
EP - 529
JO - CNS Neuroscience and Therapeutics
JF - CNS Neuroscience and Therapeutics
IS - 6
ER -