College of Pharmaceutical Science, Institute of Drug Development & Chemical Biology, Zhejiang University of Technology, Huzhou, 313200, Zhejiang, People's Republic of China.
Department of Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Huzhou, 313200, Zhejiang, People's Republic of China.
Eur J Pharmacol. 2023 Jul 5;950:175733. doi: 10.1016/j.ejphar.2023.175733. Epub 2023 Apr 26.
Glutamate dehydrogenase (GDH) is a key enzyme in mammalian glutamate metabolism. It is located at the intersection of multiple metabolic pathways and participates in a variety of cellular activities. GDH activity is strictly regulated by a variety of allosteric compounds. Here, we review the unique distribution and expressions of GDH in the brain nervous system. GDH plays an essential role in the glutamate-glutamine-GABA cycle between astrocytes and neurons. The dysfunction of GDH may induce the occurrence of many neurodegenerative diseases, such as Parkinson's disease, epilepsy, Alzheimer's disease, schizophrenia, and frontotemporal dementia. GDH activators and gene therapy have been found to protect neurons and improve motor disorders in neurodegenerative diseases caused by glutamate metabolism disorders. To date, no medicine has been discovered that specifically targets neurodegenerative diseases, although several potential medicines are used clinically. Targeting GDH to treat neurodegenerative diseases is expected to provide new insights and treatment strategies.
谷氨酸脱氢酶（GDH）是哺乳动物谷氨酸代谢中的关键酶。它位于多种代谢途径的交汇点，参与多种细胞活动。GDH 活性受到多种变构化合物的严格调节。在这里，我们回顾了 GDH 在脑神经系统中的独特分布和表达。GDH 在星形胶质细胞和神经元之间的谷氨酸-谷氨酰胺-GABA 循环中发挥着重要作用。GDH 的功能障碍可能会导致许多神经退行性疾病的发生，如帕金森病、癫痫、阿尔茨海默病、精神分裂症和额颞叶痴呆。已经发现 GDH 激活剂和基因治疗可以保护神经元并改善由谷氨酸代谢紊乱引起的神经退行性疾病中的运动障碍。迄今为止，虽然有几种潜在的药物在临床上使用，但尚未发现专门针对神经退行性疾病的药物。针对 GDH 治疗神经退行性疾病有望提供新的见解和治疗策略。
