N-Acetylaspartylglutamate (NAAG) is the third most prevalent neurotransmitter in the mammalian nervous system, yet its therapeutic potential is only now being fully recognized. Drugs that inhibit the inactivation of NAAG by glutamate carboxypeptidase II (GCPII) increase its extracellular concentration and its activation of its receptor, mGluR3. These drugs warrant attention, as they are effective in animal models of several clinical disorders including stroke, traumatic brain injury and schizophrenia. In inflammatory and neuropathic pain studies, GCPII inhibitors moderated both the primary and secondary pain responses when given systemically, locally or in brain regions associated with the pain perception pathway. The finding that GCPII inhibition also moderated the motor and cognitive effects of ethanol intoxication led to the discovery of their procognitive efficacy in long-term memory tests in control mice and in short-term memory in a mouse model of Alzheimer's disease. NAAG and GCPII inhibitors respectively reduce cocaine self-administration and the rewarding effects of a synthetic stimulant. Most recently, GCPII inhibition also has been reported to be efficacious in a model of inflammatory bowel disease. GCPII was first discovered as a protein expressed by and released from metastatic prostate cells where it is known as prostate specific membrane antigen (PSMA). GCPII inhibitors with high affinity for this protein have been developed as prostate imaging and radiochemical therapies for prostate cancer. Taken together, these data militate in favor of the development and application of GCPII inhibitors in more advanced preclinical research as a prelude to clinical trials.

中文翻译：

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N-乙酰天冬氨酰谷氨酸（NAAG）和谷氨酸羧肽酶II：丰富的肽神经递质-酶系统，具有多种临床应用。

N-乙酰丙酮酰谷氨酸（NAAG）是哺乳动物神经系统中第三种最普遍的神经递质，但是其治疗潜力直到现在才被人们充分认识。抑制谷氨酸羧肽酶II（GCPII）使NAAG失活的药物会增加其细胞外浓度及其受体mGluR3的活化。这些药物值得关注，因为它们在包括中风，脑外伤和精神分裂症在内的几种临床疾病的动物模型中均有效。在炎性和神经性疼痛研究中，当全身，局部或在与疼痛感知途径相关的大脑区域给予GCPII抑制剂时，GCPII抑制剂可缓解原发性和继发性疼痛反应。GCPII抑制作用还可以减轻乙醇中毒的运动和认知作用，这一发现导致了他们在对照组小鼠的长期记忆测试和阿尔茨海默氏病小鼠模型的短期记忆中的认知功能的发现。NAAG和GCPII抑制剂分别降低了可卡因的自我给药和合成兴奋剂的奖励作用。最近，据报道在炎症性肠疾病的模型中，GCPII抑制也是有效的。GCPII最初被发现是一种由转移性前列腺细胞表达并从其释放的蛋白质，在这里它被称为前列腺特异性膜抗原（PSMA）。对这种蛋白质具有高亲和力的GCPII抑制剂已被开发为前列腺癌的前列腺成像和放射化学疗法。在一起