Carnosine activates the CREB pathway in Caco-2 cells.

Area of Science:

• Neuroscience
• Gastroenterology
• Biochemistry

Background:

• Imidazole dipeptide carnosine (composed of β-Ala and L-His) shows potential for Alzheimer's disease treatment and cognitive function maintenance.
• Carnosine is rapidly degraded by serum carnosinase, suggesting alternative mechanisms for its brain benefits.
• Previous research indicated carnosine augments Brain-Derived Neurotrophic Factor (BDNF) expression in colorectal cancer cells.

Purpose of the Study:

• To investigate the hypothesis that carnosine improves brain function through enhanced brain-gut interaction.
• To elucidate the molecular mechanisms underlying carnosine-induced activation of brain-gut pathways.
• To explore the role of cAMP-responsive element binding protein (CREB) in carnosine's effects, given its regulation of BDNF transcription.

Main Methods:

• Investigated carnosine's effect on CREB activation and related signaling pathways.
• Examined the role of calcium (Ca2+) signaling in mediating carnosine's actions.
• Assessed carnosine's impact on the expression of CREB-regulated genes in intestinal cells.

Main Results:

• Carnosine was found to activate CREB and associated pathways.
• Activation of CREB pathways by carnosine was mediated through calcium (Ca2+)-dependent mechanisms.
• Carnosine significantly augmented the expression of CREB-regulated genes within the intestine.

Conclusions:

• Carnosine enhances the expression of CREB-regulated genes in the intestine.
• This augmentation of intestinal gene expression contributes to carnosine-mediated activation of brain-gut interaction.
• The findings provide a potential mechanism for carnosine's cognitive benefits via the gut-brain axis.