Tanaka Kohichi
Laboratory of Molecular Neuroscience, School of Biomedical Science and Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-Ku, Tokyo 113-8510, Japan.
Trends Mol Med. 2005 Jun;11(6):259-62. doi: 10.1016/j.molmed.2005.04.002.
L-glutamate is the major excitatory neurotransmitter in the brain and is responsible for normal brain function. However, high glutamate exposure triggers neuronal death, a process known as excitotoxicity. Excitotoxicity is associated with acute and chronic neurodegenerative diseases. Treating excitotoxicity using glutamate-receptor antagonists has not proven clinically viable, necessitating more sophisticated approaches. Rothstein and colleagues discovered that beta-lactam antibiotics protect neurons from excitotoxicity by increasing the number of glutamate transporters, which have a key role in clearing glutamate from the extracellular space. The design of compounds capable of modulating glutamate uptake represents a novel strategy for the treatment of neurodegenerative diseases.
L-谷氨酸是大脑中主要的兴奋性神经递质，负责大脑的正常功能。然而，高浓度的谷氨酸暴露会引发神经元死亡，这一过程被称为兴奋性毒性。兴奋性毒性与急性和慢性神经退行性疾病有关。使用谷氨酸受体拮抗剂治疗兴奋性毒性在临床上尚未被证明可行，因此需要更复杂的方法。罗斯坦及其同事发现，β-内酰胺类抗生素通过增加谷氨酸转运体的数量来保护神经元免受兴奋性毒性，谷氨酸转运体在清除细胞外空间的谷氨酸方面起着关键作用。设计能够调节谷氨酸摄取的化合物代表了一种治疗神经退行性疾病的新策略。
