谷氨酸兴奋毒性及其调节剂的研究进展

Research progress on excitotoxicity of glutamate and its modulators

兴奋性毒性主要指兴奋性神经递质谷氨酸的毒性作用,谷氨酸受体长期激活会引发一系列神经毒性,最终导致神经元功能丧失和细胞死亡。触发兴奋性毒性可能涉及谷氨酸和钙代谢的改变,谷氨酸转运蛋白、N-甲基-D-天冬氨酸受体(N-methyl-D-aspartate receptor,NMDAR)和线粒体功能障碍以及ROS的产生。该文就以上机制的发生作一综述,并简述谷氨酸兴奋毒性在精神类疾病阿尔茨海默病(Alzheimer′s disease,AD)、帕金森病(Parkinson′s disease,PD)、抑郁症(depression)和癫痫(epilepsy)中的病理机制。最后阐述广谱谷氨酸调节剂、化合物和中草药成分对谷氨酸能系统的调节作用。

Excitotoxicity mainly refers to the toxic effect of the excitatory neurotransmitter glutamate.Long-term activation of glutamate receptors will cause a series of neurotoxicity,eventually leading to the loss of neuronal function and cell death.Triggering excitotoxicity may involve changes in glutamate and calcium metabolism,dysfunction of glutamate transporter,N-methyl-D-aspartate receptor(NMDAR)and mitochondria,and production of ROS.Therefore,we here review the occurrence of these mechanisms and introduce the pathological mechanism of glutamate excitotoxicity in Alzheimer′s disease(AD),Parkinson′s disease(PD),depression and epilepsy.Finally,this review briefly describes the regulatory effects of broad-spectrum glutamic satellite modulators,marine compounds and Chinese herbal medicines on the glutamatergic system.