Advances in understanding the peptide neurotransmitter NAAG and appearance of a new member of the NAAG neuropeptide family.
Advances in understanding the peptide neurotransmitter NAAG and appearance of a new member of the NAAG neuropeptide family.
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DOI：
10.1111/j.1471-4159.2011.07338.x
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发表时间：
2011-08
影响因子：
4.7
通讯作者：
Bzdega T
中科院分区：
文献类型：
--
作者：
Neale JH;Olszewski RT;Zuo D;Janczura KJ;Profaci CP;Lavin KM;Madore JC;Bzdega T
1984年至2000年期间报道的大量数据表明，神经肽N-乙酰基谷氨酸盐（NAAG）不仅作为神经递质发挥作用，而且是哺乳动物神经系统中仅次于谷氨酸盐和GABA的第三种最普遍的递质。到2005年，通过一系列体内和体外研究进一步验证了这一结论。负责NAAG在突触释放后失活的主要酶已经被克隆、表征和敲除。这种酶的有效抑制剂已被开发出来，其功效已在一系列临床病症的动物模型中得到广泛研究，包括中风、周围神经病变、创伤性脑损伤、炎性和神经性疼痛、可卡因成瘾和精神分裂症。在进一步确定这些肽酶抑制剂在升高NAAG的突触水平中的作用机制方面也取得了相当大的进展，随后通过这种肽激活突触前mGluR 3来抑制递质释放。最近的发现包括鉴定了两种不同的神经系统酶，它们介导由N-乙酰天冬氨酸和谷氨酸合成NAAG，并且发现这些酶中的一种还介导神经肽NAAG家族的第二个成员N-乙酰天冬酰谷氨酰谷氨酸（NAAG 2）的合成。
A substantial body of data was reported between 1984 and 2000 demonstrating that the neuropeptide N-acetylaspartylglutamate (NAAG) not only functions as a neurotransmitter but also is the third most prevalent transmitter in the mammalian nervous system behind glutamate and GABA. By 2005, this conclusion was validated further through a series of studies in vivo and in vitro. The primary enzyme responsible for the inactivation of NAAG following its synaptic release had been cloned, characterized and knocked out. Potent inhibitors of this enzyme were developed and their efficacy has been extensively studied in a series of animal models of clinical conditions, including stroke, peripheral neuropathy, traumatic brain injury, inflammatory and neuropathic pain, cocaine addiction, and schizophrenia. Considerable progress also has been made in defining further the mechanism of action of these peptidase inhibitors in elevating synaptic levels of NAAG with the consequent inhibition of transmitter release via the activation of presynaptic mGluR3 by this peptide. Very recent discoveries include identification of two different nervous system enzymes that mediate the synthesis of NAAG from N-acetylaspartate and glutamate and the finding that one of these enzymes also mediates the synthesis of a second member of the NAAG family of neuropeptides, N-acetylaspartylglutamylglutamate (NAAG2).
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影响因子：
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作者：
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