Zgodova Arina, Pavlova Svetlana, Nekrasova Anastasia, Boyarkin Dmitriy, Pinelis Vsevolod, Surin Alexander, Bakaeva Zanda
Laboratory of Neurobiology and Fundamentals of Brain Development, National Medical Research Center of Children's Health, 119991 Moscow, Russia.
Department of Psychiatry and Psychosomatics, Sechenov First Moscow State Medical University (Sechenov University), 119146 Moscow, Russia.
Membranes (Basel). 2022 Oct 27;12(11):1052. doi: 10.3390/membranes12111052.
It is considered that glutamate excitotoxicity may be a major factor in the pathological death of neurons and mediate the development of neurodegenerative diseases in humans. Here, we show that isoliquiritigenin (ILG) at a concentration of 0.5-5 µM protects primary neuroglial cell culture from glutamate-induced death (glutamate 100 µM). ILG (1 µM) prevented a sharp increase in [Ca] and a decrease in mitochondrial potential (ΔΨm). With the background action of ILG (1-5 µM), there was an increase in oxygen consumption rate (OCR) in response to glutamate, as well as in reserve respiration. The neuroprotective effect of ILG (5 µM) was accompanied by an increase in non-mitochondrial respiration. The results show that ILG can protect cortical neurons from death by preventing the development of calcium deregulation and limiting mitochondrial dysfunction caused by a high dose of glutamate. We hypothesize that ILG will be useful in drug development for the prevention or treatment of neurodegenerative diseases accompanied by glutamate excitotoxicity.
人们认为谷氨酸兴奋性毒性可能是神经元病理性死亡的主要因素，并介导人类神经退行性疾病的发展。在此，我们表明浓度为0.5 - 5 µM的异甘草素（ILG）可保护原代神经胶质细胞培养物免受谷氨酸诱导的死亡（谷氨酸100 µM）。ILG（1 µM）可防止[Ca]急剧增加和线粒体膜电位（ΔΨm）降低。在ILG（1 - 5 µM）的背景作用下，谷氨酸刺激后氧消耗率（OCR）以及储备呼吸增加。ILG（5 µM）的神经保护作用伴随着非线粒体呼吸增加。结果表明，ILG可通过防止钙调节紊乱的发展和限制高剂量谷氨酸引起的线粒体功能障碍来保护皮质神经元免于死亡。我们推测ILG将有助于开发用于预防或治疗伴有谷氨酸兴奋性毒性的神经退行性疾病的药物。
