Department of Neurology and Stroke, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka-shi 350-1298, Japan.
Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Int J Mol Sci. 2021 Jun 18;22(12):6568. doi: 10.3390/ijms22126568.
Astrocytes (also, astroglia) consume huge amounts of glucose and produce lactate regardless of sufficient oxygen availability, indicating a high capacity for aerobic glycolysis. Glycolysis in astrocytes is activated in accordance with neuronal excitation and leads to increases in the release of lactate from astrocytes. Although the fate of this lactate remains somewhat controversial, it is believed to fuel neurons as an energy substrate. Besides providing lactate, astrocytic glycolysis plays an important role in neuroprotection. Among the minor pathways of glucose metabolism, glucose flux to the pentose-phosphate pathway (PPP), a major shunt pathway of glycolysis, is attracting research interest. In fact, PPP activity in astrocytes is five to seven times higher than that in neurons. The astrocytic PPP plays a key role in protecting neurons against oxidative stress by providing neurons with a reduced form of glutathione, which is necessary to eliminate reactive oxygen species. Therefore, enhancing astrocytic glycolysis might promote neuronal protection during acute ischemic stroke. Contrariwise, the dysfunction of astrocytic glycolysis and the PPP have been implicated in the pathogenesis of various neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis, since mitochondrial dysfunction and oxidative stress trigger and accelerate disease progression.
星形胶质细胞（也称为星形细胞）无论氧供应是否充足，都会大量消耗葡萄糖并产生乳酸，这表明其具有很强的有氧糖酵解能力。星形胶质细胞中的糖酵解会根据神经元的兴奋而激活，并导致乳酸从星形胶质细胞中释放增加。尽管这种乳酸的命运仍有些争议，但它被认为是神经元的能量底物。除了提供乳酸外，星形胶质细胞的糖酵解在神经保护中也起着重要作用。在葡萄糖代谢的次要途径中，葡萄糖流向戊糖磷酸途径（PPP），这是糖酵解的主要分流途径，引起了研究兴趣。实际上，星形胶质细胞中的 PPP 活性比神经元高五到七倍。星形胶质细胞的 PPP 通过提供神经元还原型谷胱甘肽来保护神经元免受氧化应激，这对于消除活性氧至关重要。因此，增强星形胶质细胞的糖酵解可能会促进急性缺血性中风期间的神经元保护。相反，星形胶质细胞糖酵解和 PPP 的功能障碍与各种神经退行性疾病（如帕金森氏病，阿尔茨海默氏病和肌萎缩性侧索硬化症）的发病机制有关，因为线粒体功能障碍和氧化应激会引发并加速疾病进展。
