Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Av. IPN 2508, San Pedro Zacatenco, 07360, CDMX, México.
Centre National de la Recherche Scientifique, Institut des Neurosciences Cellulaires et Intégratives, Université de Strasbourg, Strasbourg, France.
Neurotox Res. 2023 Feb;41(1):103-117. doi: 10.1007/s12640-022-00623-2. Epub 2023 Jan 6.
Glutamate is the major excitatory amino acid in the vertebrate brain. Glutamatergic signaling is involved in most of the central nervous system functions. Its main components, namely receptors, ion channels, and transporters, are tightly regulated at the transcriptional, translational, and post-translational levels through a diverse array of extracellular signals, such as food, light, and neuroactive molecules. An exquisite and well-coordinated glial/neuronal bidirectional communication is required for proper excitatory amino acid signal transactions. Biochemical shuttles such as the glutamate/glutamine and the astrocyte-neuronal lactate represent the fundamental involvement of glial cells in glutamatergic transmission. In fact, the disruption of any of these coordinated biochemical intercellular cascades leads to an excitotoxic insult that underlies some aspects of most of the neurodegenerative diseases characterized thus far. In this contribution, we provide a comprehensive summary of the involvement of the Aryl hydrocarbon receptor, a ligand-dependent transcription factor in the gene expression regulation of glial glutamate transporters. These receptors might serve as potential targets for the development of novel strategies for the treatment of neurodegenerative diseases.
谷氨酸是脊椎动物大脑中的主要兴奋性氨基酸。谷氨酸能信号参与了大多数中枢神经系统的功能。其主要成分,即受体、离子通道和转运体,通过多种细胞外信号(如食物、光和神经活性分子)在转录、翻译和翻译后水平上受到严格调节。适当的兴奋性氨基酸信号转导需要精细协调的胶质/神经元双向通讯。谷氨酸/谷氨酰胺和星形胶质细胞-神经元乳酸等生化穿梭物代表了胶质细胞在谷氨酸能传递中的基本参与。事实上,这些协调的细胞间生化级联反应中的任何一个中断都会导致兴奋性毒性损伤,这是迄今为止大多数神经退行性疾病的某些方面的基础。在这篇综述中,我们全面总结了芳香烃受体(一种配体依赖性转录因子)在胶质细胞谷氨酸转运体基因表达调控中的作用。这些受体可能成为开发治疗神经退行性疾病新策略的潜在靶点。