Carnosine activates the CREB pathway in Caco-2 cells.

Imidazole dipeptide, carnosine, is a versatile compound composed of β-Ala and L-His. A recent study showed that carnosine might benefit the treatment of Alzheimer's disease and the maintenance of cognitive function. Based on the observation that carnosine is immediately degraded by serum carnosinase, we hypothesized that carnosine improves brain function by promoting brain-gut interaction. This study sought to present possible mechanisms regulating carnosine-induced activation of brain-gut interaction. We had previously found that carnosine augmented the expression of BDNF in human colorectal cancer cells, thus we became interested in cAMP-responsive element binding protein (CREB), which is a dominant regulator of BDNF transcription. We found that carnosine activates CREB and CREB-related pathways by activating Ca2+-related pathways. Our findings suggest that carnosine augments the expression of CREB-regulated genes in the intestine; this augmentation contributes to the carnosine-induced activation of brain-gut interaction.