Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, United States.
Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, United States.
Int Rev Neurobiol. 2020;154:79-110. doi: 10.1016/bs.irn.2020.03.015. Epub 2020 Jul 10.
To meet its high energy demands, the brain mostly utilizes glucose. However, the brain has evolved to exploit additional fuels, such as ketones, especially during prolonged fasting. With aging and neurodegenerative diseases (NDDs), the brain becomes inefficient at utilizing glucose due to changes in glia and neurons that involve glucose transport, glycolytic and Krebs cycle enzyme activities, and insulin signaling. Positron emission tomography and magnetic resonance spectroscopy studies have identified glucose metabolism abnormalities in aging, Alzheimer's disease (AD) and other NDDs in vivo. Despite glucose hypometabolism, brain cells can utilize ketones efficiently, thereby providing a rationale for the development of therapeutic ketogenic interventions in AD and other NDDs. This review compares available ketogenic interventions and discusses the potential of the potent oral Ketone Ester for future therapeutic use in AD and other NDDs characterized by inefficient glucose utilization.
为满足其高能量需求，大脑主要利用葡萄糖。然而，大脑已经进化到可以利用其他燃料，如酮体，尤其是在长时间禁食期间。随着年龄的增长和神经退行性疾病（NDDs）的发生，由于涉及葡萄糖转运、糖酵解和克雷布斯循环酶活性以及胰岛素信号的神经胶质和神经元的变化，大脑在利用葡萄糖方面变得效率低下。正电子发射断层扫描和磁共振波谱研究在体内鉴定了衰老、阿尔茨海默病（AD）和其他 NDDs 的葡萄糖代谢异常。尽管葡萄糖代谢低下，脑细胞仍能有效地利用酮体，从而为在 AD 和其他葡萄糖利用率低下的 NDD 中开发治疗性生酮干预提供了依据。本综述比较了现有的生酮干预措施，并讨论了强效口服酮酯在未来治疗 AD 和其他以葡萄糖利用率低下为特征的 NDD 中的应用潜力。
