Table_4_ADCY3: the pivotal gene in classical ketogenic diet for the treatment of epilepsy.DOCX

ObjectiveEpilepsy is a common neurological disorder characterized by recurrent epilepsy episodes. As a non-pharmacological treatment, the ketogenic diet has been widely applied in treating epilepsy. However, the exact therapeutic mechanism of the ketogenic diet for epilepsy remains unclear. This study investigates the molecular mechanisms of the ketogenic diet in regulating fatty acid metabolism and activating the ADCY3-initiated cAMP signaling pathway to enhance neuronal inhibition and thereby treat epilepsy.
Methods and resultsMeta-analysis reveals that the ketogenic diet is superior to the conventional diet in treating epilepsy. Animal experiments demonstrate that the ketogenic diet is more effective than the conventional diet in treating epilepsy, with the best results achieved using the classic ketogenic diet. Transcriptome sequencing analysis identifies six essential genes, among which ADCY3 shows increased expression in the ketogenic diet. In vivo experiments confirm that the activation of the cAMP-PKA signaling pathway by ADCY3 enhances neuronal inhibition and improves epilepsy control.
ConclusionClinical observations indicate that the ketogenic diet improves patient epilepsy episodes by regulating the ADCY3-initiated cAMP signaling pathway.

研究目的：癫痫是一类以反复发作性癫痫发作为特征的常见神经系统疾病。生酮饮食（ketogenic diet）作为非药物治疗手段，已被广泛应用于癫痫的临床治疗。然而，生酮饮食治疗癫痫的确切分子机制仍未明确。本研究旨在探究生酮饮食调控脂肪酸代谢、激活腺苷酸环化酶3（ADCY3）介导的环磷酸腺苷（cAMP）信号通路，进而增强神经元抑制、发挥抗癫痫治疗作用的分子机制。
方法与结果：荟萃分析显示，生酮饮食在癫痫治疗效果上优于常规饮食；动物实验证实，生酮饮食的抗癫痫效果优于常规饮食，其中经典生酮饮食的治疗效果最为显著。转录组测序分析筛选得到6个核心基因，其中腺苷酸环化酶3（ADCY3）在生酮饮食干预下表达水平显著上调。体内实验进一步验证，ADCY3介导的环磷酸腺苷-蛋白激酶A（cAMP-PKA）信号通路的激活可增强神经元抑制，从而提升癫痫的病情控制效果。
结论：临床观察表明，生酮饮食可通过调控ADCY3介导的环磷酸腺苷信号通路，改善癫痫患者的发作症状。