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

Autores/as

  • Marco Machado Autor/a
  • Steven B Machek Autor/a

DOI:

https://doi.org/10.6020/85kttp31

Palabras clave:

BDNF, creatine, epigenetics, brain metabolismo, neuropharmacology, biomarker, translational research

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 creatine mediated 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 interven-
tions could be personalized through epigenetic biomarkers, offering novel opportunities for translational research and pharmaceutical innovation in the treatment of neuropsychiatric conditions.

Descargas

Los datos de descarga aún no están disponibles.

Referencias

ADRIANO, E. A. et al. Creatine as an adjunct treatment for depression in humans. Frontiers in

Nutrition, v. 5, p. 1–8, 2018. DOI: 10.3389/fnut.2018.00014.

ALLISON, J.; KALISZEWSKA, A.; UCEDA, S.; REIRIZ, M.; ARIAS, N. Targeting DNA Methylation in the

Adult Brain through Diet. Nutrients, v. 13, n. 11, p. 3979, 2021. DOI: 10.3390/nu13113979.

BRAISSANT, O.; HENRY, H.; BÉARD, E.; ULDRY, J. Creatine deficiency syndromes and the

importance of creatine synthesis in the brain. Amino Acids, v. 40, n. 5, p. 1315–1324, 2011. DOI:

10.1007/s00726-011-0874-5.

CHEN, D.; MENG, L.; PEI, F.; ZHENG, Y.; LENG, J. A review of DNA methylation in depression.

Journal of Clinical Neuroscience, v. 43, p. 39–46, 2017. DOI: 10.1016/j.jocn.2017.05.022.

DWIVEDI, Y. Involvement of brain-derived neurotrophic factor in late-life depression. American

Journal of Geriatric Psychiatry, v. 21, n. 5, p. 433–449, 2013.

JANUAR, V.; ANCELIN, M. L.; RITCHIE, K.; SAFFERY, R.; RYAN, J. BDNF promoter methylation and

genetic variation in late-life depression. Translational Psychiatry, v. 5, n. 9, e619, 2015. DOI:

10.1038/tp.2015.114.

MACHEK, S. B.; BAGLEY, J. R. Creatine Monohydrate Supplementation: Considerations for Cognitive

Performance in Athletes. Strength and Conditioning Journal, v. 40, n. 2, p. 82–93, abr 2018. DOI:

10.1519/SSC.0000000000000369.

MAROSI, K.; MATTSON, M. P. BDNF mediates adaptive brain and body responses to energetic

challenges. Trends in Endocrinology & Metabolism, v. 25, n. 2, p. 89–98, 2014. DOI:

10.1016/j.tem.2013.10.006.

NICULESCU, M. D.; ZEISEL, S. H. Diet, methyl donors and DNA methylation: Interactions between

dietary folate, methionine and choline. J Nutr, v. 132, 2333s–2335s, 2002.

PARK, C.; ROSENBLAT, J. D.; BRIETZKE, E.; PAN, Z.; LEE, Y.; MCINTYRE, R. S. Stress, epigenetics

and depression: a systematic review. Neuroscience & Biobehavioral Reviews, v. 102, p. 139–152,

2019. DOI: 10.1016/j.neubiorev.2019.04.010.

QUAIOTO, B. R. et al. Epigenetic impact of chronic stress: BDNF exon IV gene methylation in high-risk

professionals. Journal of Psychiatric Research, v. 189, p. 295–300, 2025. DOI:

10.1016/j.jpsychires.2025.06.018.

ROITMAN, S. et al. Creatine and BDNF expression in the hippocampus of rats submitted to chronic

mild stress. Behavioural Brain Research, v. 379, p. 112362, 2020. DOI:

10.1016/j.bbr.2020.112362.

ROY, B.; SHELTON, R. C.; DWIVEDI, Y. DNA methylation and expression of stress-related genes in

PBMC of MDD patients with and without serious suicidal ideation. Journal of Psychiatric Research,

v. 89, p. 115–124, 2017. DOI: 10.1016/j.jpsychires.2017.02.005.

WALLIMANN, T.; TOKARSKA-SCHLATTNER, M.; SCHLATTNER, U. The creatine kinase system and

pleiotropic effects of creatine. Amino Acids, v. 40, n. 5, p. 1271–1296, 2011. DOI:

10.1007/s00726-011-0877-2.

Descargas

Publicado

2026-08-26

Número

Sección

Articles

Cómo citar

BDNF Gene Methylation and the Creatine-Phosphate System: A Translational Perspective for Neuropharmaceutical Innovation. (2026). Interscienceplace, 21, 54-56. https://doi.org/10.6020/85kttp31