BDNF Gene Methylation and the Creatine-Phosphate System: A Translational Perspective for Neuropharmaceutical Innovation

Resumen

The maintenance of synaptic function and neuroplasticity relies on an intricate balance of
genetic, epigenetic, and metabolic factors. Brain-Derived Neurotrophic Factor (BDNF), a key protein for
neuronal health, is regulated by DNA methylation patterns that influence its expression. Concurrently,
the creatine-phosphate (PCr) system serves as a critical energy buffer, especially in the brain during
high metabolic demand. Here, we present a perspective on the potential interaction between creatinemediated BDNF gene methylation and cerebral bioenergetics. While direct mechanistic data are still lacking, emerging evidence suggests that creatine supplementation may enhance BDNF expression
and modulate synaptic energetics. These insights support the hypothesis that creatine-based interventions could be personalized through epigenetic biomarkers, offering novel opportunities for translational research and pharmaceutical innovation in the treatment of neuropsychiatric conditions.