Immunooncology Students' Science Association, Medical University of Warsaw, Żwirki i Wigury 61, Warszawa, 02-091, Poland.
Department of Neurotoxicology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawińskiego 5, Warszawa, 02-106, Poland.
Pharmacol Rep. 2024 Dec;76(6):1305-1317. doi: 10.1007/s43440-024-00644-y. Epub 2024 Sep 11.
Glutamate is the major excitatory neurotransmitter in the central nervous system (CNS). Gliomas, malignant brain tumors with a dismal prognosis, alter glutamate homeostasis in the brain, which is advantageous for their growth, survival, and invasion. Alterations in glutamate homeostasis result from its excessive production and release to the extracellular space. High glutamate concentration in the tumor microenvironment destroys healthy tissue surrounding the tumor, thus providing space for glioma cells to expand. Moreover, it confers neuron hyperexcitability, leading to epilepsy, a common symptom in glioma patients. This mini-review briefly describes the biochemistry of glutamate production and transport in gliomas as well as the activation of glutamate receptors. It also summarizes the current pre-clinical and clinical studies identifying pharmacotherapeutics targeting glutamate transporters and receptors emerging as potential therapeutic strategies for glioma.
谷氨酸是中枢神经系统（CNS）中的主要兴奋性神经递质。神经胶质瘤是一种预后不良的恶性脑肿瘤，会改变大脑中的谷氨酸稳态，这有利于它们的生长、存活和侵袭。谷氨酸稳态的改变源于其在细胞外空间的过度产生和释放。肿瘤微环境中的高谷氨酸浓度会破坏肿瘤周围的健康组织，从而为胶质瘤细胞的扩张提供空间。此外，它还会导致神经元过度兴奋，引发癫痫，这是胶质瘤患者的常见症状。这篇简要综述描述了神经胶质瘤中谷氨酸产生和转运的生物化学以及谷氨酸受体的激活。它还总结了目前针对靶向谷氨酸转运体和受体的药理学治疗的临床前和临床研究，这些研究为神经胶质瘤的潜在治疗策略提供了新的思路。
