摘要
N-乙酰天冬氨酰谷氨酸(N-acetylaspartylglutamate,NAAG)是中枢神经系统内分布最广的神经递质之一,它与突触前膜上的第Ⅱ组代谢型谷氨酸受体结合后可以抑制谷氨酸(Glu)等神经递质的释放。Glu水平的升高与神经损伤引起的疾病如创伤性脑损伤、神经病理性疼痛、精神分裂症、多发性硬化、中风、糖尿病性神经病以及阿尔采末病等密切相关。NAAG从突触释放后会被特异性的肽酶水解而失活。NAAG肽酶抑制剂可以抑制这种肽酶从而延长NAAG的活性并且对多种神经损伤疾病的动物模型均有治疗效果。该文就NAAG肽酶抑制剂在这些动物模型中的最新研究进展以及相关机制进行综述。
N-Acetylaspartylglutamate （NAAG） is one of the most abundant and widely distributed peptide transmitters in the nerv- ous system. NAAG activates the presynaptic group U metabo- tropic glutamate receptors, inhibiting the release of neurotrans- mitters, including glutamate. Elevated levels of glutamate are as- sociated with nerve injury induced pathology of traumatic brain injury （TBI）, neuropathic pain, schizophrenia, multiple sclero- sis （ MS）, stroke, diabetic neuropathy and Alzheimer＇ s dis- ease. NAAG is inactivated by specific peptidases following its synaptic release. NAAG peptidase inhibitors, which inhibit these enzymes, thus prolong the activity of synaptically released NAAG and have significant therapeutic efficacy in animal models of these diverse elinical conditions. In this review, we summarize recent studies in these animal models and discuss the mecha- nisms by which NAAG peptidase inhibitors achieve these effects.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2013年第9期1200-1204,共5页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 30871307)
江苏省自然科学基金资助项目(No BK2012580)
