Department of Pharmacology, Ajou University School of Medicine, Suwon 16499, Republic of Korea.
Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 16499, Republic of Korea.
Cells. 2024 Nov 13;13(22):1876. doi: 10.3390/cells13221876.
Glucose metabolism is essential for the maintenance and function of the central nervous system. Although the brain constitutes only 2% of the body weight, it consumes approximately 20% of the body's total energy, predominantly derived from glucose. This high energy demand of the brain underscores its reliance on glucose to fuel various functions, including neuronal activity, synaptic transmission, and the maintenance of ion gradients necessary for nerve impulse transmission. Increasing evidence shows that many neurodegenerative diseases, including Parkinson's disease (PD), are associated with abnormalities in glucose metabolism. PD is characterized by the progressive loss of dopaminergic neurons in the substantia nigra, accompanied by the accumulation of α-synuclein protein aggregates. These pathological features are exacerbated by mitochondrial dysfunction, oxidative stress, and neuroinflammation, all of which are influenced by glucose metabolism disruptions. Emerging evidence suggests that targeting glucose metabolism could offer therapeutic benefits for PD. Several antidiabetic drugs have shown promise in animal models and clinical trials for mitigating the symptoms and progression of PD. This review explores the current understanding of the association between PD and glucose metabolism, emphasizing the potential of antidiabetic medications as a novel therapeutic approach. By improving glucose uptake and utilization, enhancing mitochondrial function, and reducing neuroinflammation, these drugs could address key pathophysiological mechanisms in PD, offering hope for more effective management of this debilitating disease.
葡萄糖代谢对于中枢神经系统的维持和功能至关重要。尽管大脑仅占体重的 2%，但它消耗了大约 20%的身体总能量，主要来源于葡萄糖。大脑的高能量需求突显了其对葡萄糖的依赖，以提供各种功能所需的能量，包括神经元活动、突触传递以及维持神经冲动传递所需的离子梯度。越来越多的证据表明，许多神经退行性疾病，包括帕金森病（PD），与葡萄糖代谢异常有关。PD 的特征是黑质中多巴胺能神经元的进行性丧失，伴随着α-突触核蛋白聚集体的积累。这些病理特征因线粒体功能障碍、氧化应激和神经炎症而加剧，所有这些都受到葡萄糖代谢紊乱的影响。新出现的证据表明，靶向葡萄糖代谢可能为 PD 提供治疗益处。几种抗糖尿病药物在动物模型和临床试验中显示出减轻 PD 症状和进展的潜力。本综述探讨了 PD 与葡萄糖代谢之间的关联的现有理解，强调了抗糖尿病药物作为一种新的治疗方法的潜力。通过改善葡萄糖摄取和利用、增强线粒体功能和减少神经炎症，这些药物可以针对 PD 的关键病理生理机制，为更有效地管理这种使人衰弱的疾病带来希望。
