Limón-Pacheco Jorge H, Gonsebatt María E
Departamento de Neurobiología Conductual y Cognitiva, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Boulevard Juriquilla 3001, Querétaro, México.
Cent Nerv Syst Agents Med Chem. 2010 Dec 1;10(4):287-97. doi: 10.2174/187152410793429683.
The glutathione system includes reduced (GSH) and oxidized (GSSG) forms of glutathione; the enzymes required for its synthesis and recycling, such as gamma-glutamate cysteine ligase (γ-GCL), glutathione synthetase (GS), glutathione reductase (GSR) and gamma glutamyl transpeptidase (γ-GGT); and the enzymes required for its use in metabolism and in mechanisms of defense against free radical-induced oxidative damage, such as glutathione s-transferases (GSTs) and glutathione peroxidases (GPxs). Glutathione functions in the central nervous system (CNS) include maintenance of neurotransmitters, membrane protection, detoxification, metabolic regulation, and modulation of signal transduction. A common pathological hallmark in various neurodegenerative disorders, such as amyotrophic lateral sclerosis and Alzheimer's and Parkinson's diseases is the increase in oxidative stress and the failure of antioxidant systems, such as the decrease in the GSH content. The administration of exogenous neurohormone melatonin at pharmacological doses has been shown not only to be an effective scavenger of reactive oxygen and nitrogen species but also to enhance the levels of GSH and the expression and activities of the GSH-related enzymes including γ-GCL, GPxs, and GSR. The exact mechanisms by which melatonin regulates the glutathione system are not fully understood. The main purpose of this short review is to discuss evidence relating to the potential common modulation signals between the glutathione system and melatonin in the CNS. The potential regulatory mechanisms and interactions between neurons and non-neuronal cells are also discussed.
谷胱甘肽系统包括还原型（GSH）和氧化型（GSSG）谷胱甘肽；其合成和循环所需的酶，如γ-谷氨酰半胱氨酸连接酶（γ-GCL）、谷胱甘肽合成酶（GS）、谷胱甘肽还原酶（GSR）和γ-谷氨酰转肽酶（γ-GGT）；以及其在代谢和抵御自由基诱导的氧化损伤机制中使用所需的酶，如谷胱甘肽S-转移酶（GSTs）和谷胱甘肽过氧化物酶（GPxs）。谷胱甘肽在中枢神经系统（CNS）中的功能包括维持神经递质、保护细胞膜、解毒、代谢调节和信号转导调节。各种神经退行性疾病，如肌萎缩侧索硬化症、阿尔茨海默病和帕金森病的一个共同病理特征是氧化应激增加和抗氧化系统功能障碍，如谷胱甘肽含量降低。药理学剂量的外源性神经激素褪黑素不仅已被证明是活性氧和氮物种的有效清除剂，而且还能提高谷胱甘肽水平以及包括γ-GCL、GPxs和GSR在内的谷胱甘肽相关酶的表达和活性。褪黑素调节谷胱甘肽系统的确切机制尚未完全了解。这篇简短综述的主要目的是讨论中枢神经系统中谷胱甘肽系统和褪黑素之间潜在的共同调节信号的相关证据。还讨论了神经元与非神经元细胞之间潜在的调节机制和相互作用。
