Key Laboratory of Neuroscience, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China.
Department of Traditional Chinese Medicine, School of Medicine, Xiamen University, Xiamen 361102, China.
Curr Neuropharmacol. 2020;18(4):260-276. doi: 10.2174/1570159X17666191101125530.
Glutamate is the major excitatory neurotransmitter in the central nervous system, and its signaling is critical for excitatory synaptic transmission. The well-established glutamate system involves glutamate synthesis, presynaptic glutamate release, glutamate actions on the ionotropic glutamate receptors (NMDA, AMPA, and kainate receptors) and metabotropic glutamate receptors, and glutamate uptake by glutamate transporters. When the glutamate system becomes dysfunctional, it contributes to the pathogenesis of neurodegenerative and neuropsychiatric diseases such as Alzheimer's disease, Parkinson's disease, depression, epilepsy, and ischemic stroke. In this review, based on regulating glutamate signaling, we summarize the effects and underlying mechanisms of natural constituents from Chinese herbal medicines on neurological disorders. Natural constituents from Chinese herbal medicine can prevent the glutamate-mediated excitotoxicity via suppressing presynaptic glutamate release, decreasing ionotropic and metabotropic glutamate receptors expression in the excitatory synapse, and promoting astroglial glutamate transporter expression to increase glutamate clearance from the synaptic cleft. However, some natural constituents from Chinese herbal medicine have the ability to restore the collapse of excitatory synapses by promoting presynaptic glutamate release and increasing ionotropic and metabotropic glutamate receptors expression. These regulatory processes involve various signaling pathways, which lead to different mechanistic routes of protection against neurological disorders. Hence, our review addresses the underlying mechanisms of natural constituents from Chinese herbal medicines that regulate glutamate systems and serve as promising agents for the treatment of the above-mentioned neurological disorders.
谷氨酸是中枢神经系统中的主要兴奋性神经递质，其信号转导对于兴奋性突触传递至关重要。成熟的谷氨酸系统包括谷氨酸的合成、突触前谷氨酸的释放、谷氨酸对离子型谷氨酸受体（NMDA、AMPA 和 kainate 受体）和代谢型谷氨酸受体的作用，以及谷氨酸转运体对谷氨酸的摄取。当谷氨酸系统功能失调时，会导致神经退行性和神经精神疾病的发病机制，如阿尔茨海默病、帕金森病、抑郁症、癫痫和缺血性中风。在这篇综述中，我们基于调节谷氨酸信号转导，总结了中草药天然成分对神经紊乱的作用及其潜在机制。中草药天然成分可以通过抑制突触前谷氨酸释放、减少兴奋性突触中离子型和代谢型谷氨酸受体的表达，以及促进星形胶质细胞谷氨酸转运体的表达，来防止谷氨酸介导的兴奋性毒性，从而增加从突触间隙清除谷氨酸。然而，一些中草药天然成分具有通过促进突触前谷氨酸释放和增加离子型和代谢型谷氨酸受体的表达来恢复兴奋性突触崩溃的能力。这些调节过程涉及多种信号通路，导致了针对上述神经紊乱的不同保护机制途径。因此，我们的综述探讨了调节谷氨酸系统的中草药天然成分的潜在机制，并为治疗上述神经紊乱提供了有前途的药物。
