Department of Biology, University of Padova, Padova, Italy.
Department of Biomedical Sciences, University of Padova, Padova, Italy; Neuroscience Institute, National Research Council (CNR), Padua, Italy.
Trends Neurosci. 2021 May;44(5):342-351. doi: 10.1016/j.tins.2021.01.001. Epub 2021 Feb 16.
Excitotoxicity is likely to occur in pathological scenarios in which mitochondrial function is already compromised, shaping neuronal responses to glutamate. In fact, mitochondria sustain cell bioenergetics, tune intracellular Ca dynamics, and regulate glutamate availability by using it as metabolic substrate. Here, we suggest the need to explore glutamate toxicity in the context of specific disease models in which it may occur, re-evaluating the impact of mitochondrial dysfunction on glutamate excitotoxicity. Our aim is to signpost new approaches, perhaps combining glutamate and pathways to rescue mitochondrial function, as therapeutic targets in neurological disorders.
兴奋性毒性可能发生在已经受损的线粒体功能的病理情况下，从而影响神经元对谷氨酸的反应。实际上，线粒体通过将谷氨酸作为代谢底物来维持细胞的生物能量学，调节细胞内 Ca 动力学，并调节谷氨酸的可用性。在这里，我们建议有必要在可能发生谷氨酸毒性的特定疾病模型中探索谷氨酸毒性，重新评估线粒体功能障碍对谷氨酸兴奋性毒性的影响。我们的目标是为神经疾病的治疗靶点指明新的方法，也许可以将谷氨酸和挽救线粒体功能的途径结合起来。
