Roles of glutamine synthetase inhibition in epilepsy.
Roles of glutamine synthetase inhibition in epilepsy.
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DOI：
10.1007/s11064-012-0766-5
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发表时间：
2012-11
影响因子：
4.4
通讯作者：
Lee, Tih-Shih W.
中科院分区：
文献类型：
--
作者：
Eid, Tore;Behar, Kevin;Dhaher, Ronnie;Bumanglag, Argyle V.;Lee, Tih-Shih W.
谷氨酰胺合成酶（GS，EC 6.3.1.2）是一种普遍存在且高度区室化的酶，其关键性地参与脑中的几种代谢途径，包括谷氨酰胺-谷氨酸-GABA循环和氨的解毒。GS通常定位于大多数星形胶质细胞的细胞质中，在血管周围的终足和靠近兴奋性突触的过程中存在浓度升高的酶。有趣的是，越来越多的研究表明，脑GS的表达，分布或活性在几种脑疾病，包括阿尔茨海默病，精神分裂症，抑郁症，自杀，和内侧颞叶癫痫（MTLE）中改变。虽然脑GS扰动的代谢和功能后遗症尚未完全了解，但由于酶的关键代谢作用，脑GS的缺乏可能会产生显著的生物学影响。此外，缺乏该酶的星形胶质细胞中GS的恢复可能构成针对这些疾病的新型且高度特异性的疗法。这篇综述的目的是总结哺乳动物GS在正常情况下的主要特征，并讨论GS缺乏在脑疾病，特别是MTLE的后果。
Glutamine synthetase (GS, E.C. 6.3.1.2) is a ubiquitous and highly compartmentalized enzyme that is critically involved in several metabolic pathways in the brain, including the glutamine-glutamate-GABA cycle and detoxification of ammonia. GS is normally localized to the cytoplasm of most astrocytes, with elevated concentrations of the enzyme being present in perivascular endfeet and in processes close to excitatory synapses. Interestingly, an increasing number of studies have indicated that the expression, distribution, or activity of brain GS is altered in several brain disorders, including Alzheimer’s disease, schizophrenia, depression, suicidality, and mesial temporal lobe epilepsy (MTLE). Although the metabolic and functional sequelae of brain GS perturbations are not fully understood, it is likely that a deficiency in brain GS will have a significant biological impact due to the critical metabolic role of the enzyme. Furthermore, it is possible that restoration of GS in astrocytes lacking the enzyme could constitute a novel and highly specific therapy for these disorders. The goals of this review are to summarize key features of mammalian GS under normal conditions, and discuss the consequences of GS deficiency in brain disorders, specifically MTLE.
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影响因子：
2.9
作者：
Bernard-Hélary, K;Ardourel, MY;Cloix, JF
通讯作者：
Cloix, JF
影响因子：
6.3
作者：
Dalsgaard, Mads K.;Madsen, Flemming F.;Quistorff, Bjorn
通讯作者：
Quistorff, Bjorn
DOI：
10.1073/pnas.89.6.2115
发表时间：
1992-03-15
影响因子：
11.1
作者：
BU, DF;ERLANDER, MG;TOBIN, AJ
通讯作者：
TOBIN, AJ
影响因子：
5.6
作者：
Cremer, Christian M.;Bidmon, Hans-Juergen;Zilles, Karl
通讯作者：
Zilles, Karl
影响因子：
2.5
作者：
BLONDET, B;HANTAZAMBROISE, D;RIEGER, F
通讯作者：
RIEGER, F