Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India.
J Neurosci Res. 2021 Dec;99(12):3148-3189. doi: 10.1002/jnr.24977. Epub 2021 Nov 8.
The imbalance between glutamate and γ-aminobutyric acid (GABA) results in the loss of synaptic strength leading to neurodegeneration. The dogma on the field considered neurons as the main players in this excitation-inhibition (E/I) balance. However, current strategies focusing only on neurons have failed to completely understand this condition, bringing up the importance of glia as an alternative modulator for neuroinflammation as glia alter the activity of neurons and is a source of both neurotrophic and neurotoxic factors. This review's primary goal is to illustrate the role of glia over E/I balance in the central nervous system and its interaction with neurons. Rather than focusing only on the neuronal targets, we take a deeper look at glial receptors and proteins that could also be explored as drug targets, as they are early responders to neurotoxic insults. This review summarizes the neuron-glia interaction concerning GABA and glutamate, possible targets, and its involvement in the E/I imbalance in neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis.
谷氨酸和γ-氨基丁酸(GABA)之间的失衡导致突触强度丧失,从而导致神经退行性变。该领域的教条认为神经元是这种兴奋-抑制(E/I)平衡的主要参与者。然而,目前仅关注神经元的策略未能完全理解这种情况,突显了神经胶质作为神经炎症替代调节剂的重要性,因为神经胶质改变神经元的活性,是神经营养和神经毒性因子的来源。本综述的主要目的是说明中枢神经系统中神经胶质在 E/I 平衡中的作用及其与神经元的相互作用。我们不仅关注神经元靶标,还更深入地研究神经胶质受体和蛋白,因为它们是神经毒性损伤的早期反应者,也可以作为药物靶点进行探索。本综述总结了涉及 GABA 和谷氨酸的神经元-神经胶质相互作用、可能的靶点,以及其在阿尔茨海默病、帕金森病、亨廷顿病和多发性硬化症等神经退行性疾病中的 E/I 失衡中的作用。