大脑中的 AMPK：它在葡萄糖和神经代谢中的作用,The FEBS Journal

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大脑中的 AMPK：它在葡萄糖和神经代谢中的作用
The FEBS Journal ( IF 5.5 ) Pub Date : 2021-08-06 , DOI: 10.1111/febs.16151
Ranjithmenon Muraleedharan ₁ , Biplab Dasgupta ₂

Affiliation

腺苷一磷酸活化蛋白激酶 (AMPK) 是一种综合代谢传感器，可在细胞水平上维持能量平衡，并在协调组织间代谢信号传导中发挥重要作用。AMPK 基本调节细胞存活、代谢和细胞稳态以及对各种代谢应激的反应。迄今为止的研究表明，AMPK 通路与神经退行性变和 CNS 病理学有关，但所涉及的机制仍不清楚。AMPK 失调在神经退行性疾病中已有报道，例如肌萎缩侧索硬化症、多发性硬化症、阿尔茨海默病、帕金森病、亨廷顿病和其他神经病。AMPK 激活似乎既具有神经保护作用又具有促凋亡作用，可能取决于神经细胞类型、损伤的性质、以及 AMPK 激活的强度和持续时间。虽然 AMPK 缺失小鼠的胚胎大脑发育似乎正常进行，没有任何明显的结构异常，但我们最近的研究证实了 AMPK 缺失对产后和衰老大脑的全面影响。我们的研究表明，神经元中的 Ampk 缺失增加了基础神经元的兴奋性并减少了刺激后癫痫发作的潜伏期。三个主要途径，糖酵解、磷酸戊糖分流和糖原转换，有助于大脑中葡萄糖的利用。AMPK 在星形胶质细胞代谢中对有氧糖酵解的调节值得进一步考虑，特别是糖原转换以及在激活过程中葡萄糖和糖原衍生的乳酸从星形胶质细胞到神经元的穿梭。在这篇小评论中，我们关注 AMPK 和大脑能量感应的最新进展。

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AMPK in the brain: its roles in glucose and neural metabolism

The adenosine monophosphate-activated protein kinase (AMPK) is an integrative metabolic sensor that maintains energy balance at the cellular level and plays an important role in orchestrating intertissue metabolic signaling. AMPK regulates cell survival, metabolism, and cellular homeostasis basally as well as in response to various metabolic stresses. Studies so far show that the AMPK pathway is associated with neurodegeneration and CNS pathology, but the mechanisms involved remain unclear. AMPK dysregulation has been reported in neurodegenerative diseases such as amyotrophic lateral sclerosis, multiple sclerosis, Alzheimer's disease, Parkinson's disease, Huntington's disease, and other neuropathies. AMPK activation appears to be both neuroprotective and pro-apoptotic, possibly dependent upon neural cell types, the nature of insults, and the intensity and duration of AMPK activation. While embryonic brain development in AMPK null mice appears to proceed normally without any overt structural abnormalities, our recent study confirmed the full impact of AMPK loss in the postnatal and aging brain. Our studies revealed that Ampk deletion in neurons increased basal neuronal excitability and reduced latency to seizure upon stimulation. Three major pathways, glycolysis, pentose phosphate shunt, and glycogen turnover, contribute to utilization of glucose in the brain. AMPK’s regulation of aerobic glycolysis in astrocytic metabolism warrants further deliberation, particularly glycogen turnover and shuttling of glucose- and glycogen-derived lactate from astrocytes to neurons during activation. In this minireview, we focus on recent advances in AMPK and energy-sensing in the brain.

更新日期：2021-08-06

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