Department of Biology, Georgetown University, Washington, DC, USA.
Neurobiol Learn Mem. 2019 Feb;158:9-13. doi: 10.1016/j.nlm.2019.01.006. Epub 2019 Jan 7.
The peptide transmitter N-acetylaspartylglutamate (NAAG) and its receptor, the type 3 metabotropic glutamate receptor (mGluR3, GRM3), are prevalent and widely distributed in the mammalian nervous system. Drugs that inhibit the inactivation of synaptically released NAAG have procognitive activity in object recognition and other behavioral models. These inhibitors also reverse cognitive deficits in animal models of clinical disorders. Antagonists of mGluR3 block these actions and mice that are null mutant for this receptor are insensitive to the actions of these procognitive drugs. A positive allosteric modulator of this receptor also has procognitive activity. While some data suggest that drugs acting on mGluR3 achieve their procognitive action by increasing arousal during acquisition training, exploration of the procognitive efficacy of NAAG is in its early stages and thus substantial opportunities exist to define the breadth and nature of this activity.
肽递质 N-乙酰天冬氨酸谷氨酸盐（NAAG）及其受体，代谢型谷氨酸受体 3（mGluR3，GRM3），在哺乳动物神经系统中普遍存在且广泛分布。抑制突触释放的 NAAG 失活的药物在物体识别和其他行为模型中具有认知促进作用。这些抑制剂还可逆转临床疾病动物模型中的认知缺陷。mGluR3 的拮抗剂可阻断这些作用，并且该受体的缺失突变小鼠对这些认知促进药物的作用不敏感。该受体的正变构调节剂也具有认知促进作用。虽然一些数据表明，作用于 mGluR3 的药物通过在获得性训练期间增加唤醒来发挥其认知促进作用，但 NAAG 的认知促进作用仍处于早期阶段，因此有很大的机会可以确定这种活性的广度和性质。
