Glutamate, glutamate receptors, and downstream signaling pathways.
Glutamate, glutamate receptors, and downstream signaling pathways.
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DOI：
10.7150/ijbs.6426
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发表时间：
2013
影响因子：
9.2
通讯作者：
Koochekpour S
中科院分区：
文献类型：
--
作者：
Willard SS;Koochekpour S
谷氨酸是一种非必需氨基酸，是正常细胞和肿瘤细胞增殖的主要生物能底物，也是一种兴奋性神经递质，积极参与生物合成、生物能、代谢和致癌信号通路。谷氨酸信号激活了一个由代谢性谷氨酸受体（mGluRs）和嗜离子性谷氨酸受体（iGluRs）组成的受体家族，这两种受体都与慢性致残性脑疾病（如精神分裂症）和神经退行性疾病（如阿尔茨海默病、帕金森病和多发性硬化症）有关。本文就mGluRs和iGluRs的结构和功能关系及其下游信号通路进行综述。我们将详细讨论三组mGluRs、相关的第二信使系统以及随后的PI3K/Akt、MAPK、NFkB、PLC和Ca/CaM信号系统的激活。将重点介绍人类mGluR1a作为I-mGluRs最重要的同工异构体之一的现状。概述了mGluRs家族人类同源物研究的不足。我们的结论是，经过进一步的研究，人类谷氨酸启动的信号通路可能为各种非恶性和恶性人类疾病提供新的治疗机会。
Glutamate is a nonessential amino acid, a major bioenergetic substrate for proliferating normal and neoplastic cells, and an excitatory neurotransmitter that is actively involved in biosynthetic, bioenergetic, metabolic, and oncogenic signaling pathways. Glutamate signaling activates a family of receptors consisting of metabotropic glutamate receptors (mGluRs) and ionotropic glutamate receptors (iGluRs), both of which have been implicated in chronic disabling brain disorders such as Schizophrenia and neurodegenerative diseases like Alzheimer's, Parkinson's, and multiple sclerosis. In this review, we discuss the structural and functional relationship of mGluRs and iGluRs and their downstream signaling pathways. The three groups of mGluRs, the associated second messenger systems, and subsequent activation of PI3K/Akt, MAPK, NFkB, PLC, and Ca/CaM signaling systems will be discussed in detail. The current state of human mGluR1a as one of the most important isoforms of Group I-mGluRs will be highlighted. The lack of studies on the human orthologues of mGluRs family will be outlined. We conclude that upon further study, human glutamate-initiated signaling pathways may provide novel therapeutic opportunities for a variety of non-malignant and malignant human diseases.
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影响因子：
16.2
作者：
ARAMORI, I;NAKANISHI, S
通讯作者：
NAKANISHI, S
DOI：
10.1523/jneurosci.2456-10.2011
发表时间：
2011-04-06
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Boersma MC;Dresselhaus EC;De Biase LM;Mihalas AB;Bergles DE;Meffert MK
通讯作者：
Meffert MK
影响因子：
4.8
作者：
Francesconi, A;Duvoisin, RM
通讯作者：
Duvoisin, RM
影响因子：
16.2
作者：
Beneken, J;Tu, JC;Leahy, DJ
通讯作者：
Leahy, DJ
影响因子：
12.4
作者：
Allen, JW;Knoblach, SM;Faden, A
通讯作者：
Faden, A