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. Author manuscript; available in PMC: 2023 Jun 12.
Published in final edited form as: Nat Rev Neurol. 2022 Mar 31;18(6):333–347. doi: 10.1038/s41582-022-00651-8

Figure 2: Epilepsy Treatment Targets in the Pyramid of Life.

Figure 2:

Traditional drug targets are only found at the top of the pyramid, whereas metabolic therapies are uniquely positioned to reset fundamental self-regulatory mechanisms that form functional homeostatic systems. Primordial metabolites such as adenosine and ATP are essential components of complex biochemical networks and represent the foundation for simple metabolism-based regulatory systems to enable energy homeostasis. The evolution of life required the advent of RNA, peptides and proteins, which established the framework for bioenergetics and metabolism. This was followed later by DNA and gene regulatory mechanisms such as epigenetic modifications or use of non-coding RNAs. Transcription factors provided further refinement to these mechanisms. Finally, regulatory systems based on G protein-coupled receptors (GPCRs), ion channels, and protein kinases evolved. From this schema, it becomes evident that if fundamental mechanisms at the base of the pyramid are disrupted, disease can result. Modified from Boison D, The Biochemistry and Epigenetics of Epilepsy: Focus on Adenosine and Glycine, Frontiers in Molecular Neuroscience 2016; 9:26. doi: 10.3389/fnmol.2016.00026.