Liraglutide Promotes Cortical Neurite Outgrowth via the MEK–ERK Pathway

Liraglutide is the glucagon-like peptide-1 (GLP-1) synthetic form which has been approved by the US Food and Drug Administration to be released onto the market. The metabolic benefits of incretin hormone as an anti-diabetic agent are widely recognized, but its potential extra-pancreatic effects of GLP-1 analog (liraglutide) in the central nerve system are less well known. To this purpose, we used immunofluorescence method to examine the effect of liraglutide on neurite outgrowth in primary cortical neuron culture by measuring neurite length and confirmed the promotion effect. Then, we investigated the potential mechanisms and found that liraglutide promoted neurite outgrowth in a dose-dependant manner, and this effect could be partially inhibited by MEK–ERK inhibitor U0126. Besides, liraglutide induced an increase of p-ERK/ERK expression, which could be blocked in the presence of U0126. Similarly, phosphorylated transcription factor (p-CREB) level shared the same trend with p-ERK/ERK ratio after liraglutide treatment. Collectively, our data illustrated that that liraglutide exerts neurotrophin-like activity partly via MEK–ERK pathway, which might offer a novel idea for treatment of axon-associated neurological diseases.