Chi-Castañeda Donají, Ortega Arturo
Laboratorio de Neurotoxicología, Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico.
Front Endocrinol (Lausanne). 2018 Jun 21;9:340. doi: 10.3389/fendo.2018.00340. eCollection 2018.
L-glutamate is the major excitatory amino acid in the mammalian central nervous system (CNS). This neurotransmitter is essential for higher brain functions such as learning, cognition and memory. A tight regulation of extra-synaptic glutamate levels is needed to prevent a neurotoxic insult. Glutamate removal from the synaptic cleft is carried out by a family of sodium-dependent high-affinity transporters, collectively known as excitatory amino acid transporters. Dysfunction of glutamate transporters is generally involved in acute neuronal injury and neurodegenerative diseases, so characterizing and understanding the mechanisms that lead to the development of these disorders is an important goal in the design of novel treatments for the neurodegenerative diseases. Increasing evidence indicates glutamate transporters are controlled by the circadian system in direct and indirect manners, so in this contribution we focus on the mechanisms of circadian regulation (transcriptional, translational, post-translational and post-transcriptional regulation) of glutamate transport in neuronal and glial cells, and their consequence in brain function.
L-谷氨酸是哺乳动物中枢神经系统(CNS)中的主要兴奋性氨基酸。这种神经递质对于学习、认知和记忆等高级脑功能至关重要。需要严格调节突触外谷氨酸水平以防止神经毒性损伤。从突触间隙清除谷氨酸是由一族钠依赖性高亲和力转运体完成的,这些转运体统称为兴奋性氨基酸转运体。谷氨酸转运体功能障碍通常与急性神经元损伤和神经退行性疾病有关,因此表征和理解导致这些疾病发生的机制是设计神经退行性疾病新疗法的一个重要目标。越来越多的证据表明谷氨酸转运体受昼夜节律系统直接或间接控制,因此在本论文中,我们聚焦于神经元和神经胶质细胞中谷氨酸转运的昼夜节律调节机制(转录、翻译、翻译后和转录后调节)及其对脑功能的影响。