Newington Jordan T, Harris Richard A, Cumming Robert C
Department of Biology, The University of Western Ontario, London, ON, Canada N6A 5B7.
J Neurodegener Dis. 2013;2013:234572. doi: 10.1155/2013/234572. Epub 2013 Apr 23.
The conventional view of central nervous system (CNS) metabolism is based on the assumption that glucose is the main fuel source for active neurons and is processed in an oxidative manner. However, since the early 1990s research has challenged the idea that the energy needs of nerve cells are met exclusively by glucose and oxidative metabolism. This alternative view of glucose utilization contends that astrocytes metabolize glucose to lactate, which is then released and taken up by nearby neurons and used as a fuel source, commonly known as the astrocyte-neuron lactate shuttle (ANLS) model. Once thought of as a waste metabolite, lactate has emerged as a central player in the maintenance of neuronal function and long-term memory. Decreased neuronal metabolism has traditionally been viewed as a hallmark feature of Alzheimer's disease (AD). However, a more complex picture of CNS metabolism is emerging that may provide valuable insight into the pathophysiological changes that occur during AD and other neurodegenerative diseases. This review will examine the ANLS model and present recent evidence highlighting the critical role that lactate plays in neuronal survival and memory. Moreover, the role of glucose and lactate metabolism in AD will be re-evaluated from the perspective of the ANLS.
中枢神经系统（CNS）代谢的传统观点基于这样一种假设，即葡萄糖是活跃神经元的主要燃料来源，并以氧化方式进行处理。然而，自20世纪90年代初以来，研究对神经细胞的能量需求仅由葡萄糖和氧化代谢来满足这一观点提出了挑战。这种关于葡萄糖利用的另一种观点认为，星形胶质细胞将葡萄糖代谢为乳酸，然后乳酸被释放出来并被附近的神经元摄取，用作燃料来源，这就是通常所说的星形胶质细胞-神经元乳酸穿梭（ANLS）模型。乳酸曾经被认为是一种废物代谢产物，但现在已成为维持神经元功能和长期记忆的核心因素。传统上，神经元代谢降低被视为阿尔茨海默病（AD）的一个标志性特征。然而，中枢神经系统代谢的情况正变得更加复杂，这可能为深入了解AD和其他神经退行性疾病过程中发生的病理生理变化提供有价值的见解。这篇综述将探讨ANLS模型，并展示近期证据，突出乳酸在神经元存活和记忆中所起的关键作用。此外，将从ANLS的角度重新评估葡萄糖和乳酸代谢在AD中的作用。
