Psychology Department, Trinity College, 300 Summit St., Hartford, CT, USA.
Curr Neuropharmacol. 2009 Sep;7(3):257-68. doi: 10.2174/157015909789152164.
For many years the neuromodulator adenosine has been recognized as an endogenous anticonvulsant molecule and termed a "retaliatory metabolite." As the core molecule of ATP, adenosine forms a unique link between cell energy and neuronal excitability. In parallel, a ketogenic (high-fat, low-carbohydrate) diet is a metabolic therapy that influences neuronal activity significantly, and ketogenic diets have been used successfully to treat medically-refractory epilepsy, particularly in children, for decades. To date the key neural mechanisms underlying the success of dietary therapy are unclear, hindering development of analogous pharmacological solutions. Similarly, adenosine receptor-based therapies for epilepsy and myriad other disorders remain elusive. In this review we explore the physiological regulation of adenosine as an anticonvulsant strategy and suggest a critical role for adenosine in the success of ketogenic diet therapy for epilepsy. While the current focus is on the regulation of adenosine, ketogenic metabolism and epilepsy, the therapeutic implications extend to acute and chronic neurological disorders as diverse as brain injury, inflammatory and neuropathic pain, autism and hyperdopaminergic disorders. Emerging evidence for broad clinical relevance of the metabolic regulation of adenosine will be discussed.
多年来，神经调质腺苷一直被认为是一种内源性抗惊厥分子，并被称为“报复性代谢产物”。作为 ATP 的核心分子，腺苷在细胞能量和神经元兴奋性之间形成了独特的联系。与此同时，生酮饮食（高脂肪、低碳水化合物）是一种代谢疗法，它可以显著影响神经元活动，并且生酮饮食已成功用于治疗医学上难治性癫痫，尤其是在儿童中，已有数十年的历史。迄今为止，饮食疗法成功的关键神经机制尚不清楚，这阻碍了类似的药理学解决方案的发展。同样，基于腺苷受体的癫痫和无数其他疾病的治疗方法仍然难以捉摸。在这篇综述中，我们探讨了腺苷作为抗惊厥策略的生理调节，并提出了腺苷在生酮饮食治疗癫痫中的关键作用。虽然目前的重点是腺苷、生酮代谢和癫痫的调节，但治疗意义还扩展到了从脑损伤、炎症和神经痛、自闭症到高多巴胺能障碍等各种急性和慢性神经疾病。我们将讨论新兴的证据表明，代谢调节腺苷具有广泛的临床相关性。
