Effects of TND1128 (a 5-deazaflavin derivative), with self-redox ability, as a mitochondria activator on the mouse brain slice and its comparison with β-NMN
Effects of TND1128 (a 5-deazaflavin derivative), with self-redox ability, as a mitochondria activator on the mouse brain slice and its comparison with β-NMN
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具有自氧化还原能力的TND1128（5-脱氮黄素衍生物）作为线粒体激活剂对小鼠脑切片的影响及其与β-NMN的比较
DOI：
10.1016/j.jphs.2022.11.005
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Yoshihisa Kudo
中科院分区：
文献类型：
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作者：
Nanae Takahashi;Norio Akaike;Tomohisa Nagamatsu;Hiroyuki Uchino;Yoshihisa Kudo
我们没有明确的治疗痴呆症的特点是长期的神经元死亡，由于大量积累的外来物质，如β-淀粉样蛋白。由于阿尔茨海默型痴呆症发展缓慢，我们可能能够通过增强单个神经元的能量代谢来延迟发作并改善神经元功能障碍。TND 1128是5-脱氮黄素的衍生物，是已知具有有效的自氧化还原能力的化学品。我们预期TND 1128作为线粒体能量合成的激活剂。我们使用从用TND 1128或β-NMN预处理22 ± 2小时的小鼠制备的脑切片。用荧光钙指示剂Fura-4F和X-Rhod-1分别测定细胞质和线粒体内钙离子浓度，并通过重复80 K暴露，观察药物对细胞质和线粒体内钙超载的保护作用。TND 1128（0.01、0.1和1 mg/kg s.c.）以剂量依赖性方式缓解[Ca 2 +]细胞和[Ca 2 +]的动态变化。β-NMN（10、30和100 mg/kg s.c.）对细胞胞浆内[Ca ~（2+）]_（cyt）也有明显的剂量依赖性的抑制作用，但对线粒体[Ca ~（2+）]_（m）动力学的影响不明显。在本研究中，我们证实了TND 1128的激活神经元的潜力。我们期望TND 1128作为一种药物，可以挽救衰老或疾病引起的神经元退化。
We have no definitive treatment for dementia characterized by prolonged neuronal death due to the enormous accumulation of foreign matter, such as β-amyloid. Since Alzheimer's type dementia develops slowly, we may be able to delay the onset and improve neuronal dysfunction by enhancing the energy metabolism of individual neurons. TND1128, a derivative of 5-deazaflavin, is a chemical known to have an efficient self-redox ability. We expected TND1128 as an activator for mitochondrial energy synthesis. We used brain slices prepared from mice 22 ± 2 h pretreated with TND1128 or β-NMN. We measured Ca2+concentrations in the cytoplasm ([Ca2+]cyt) and mitochondria ([Ca2+]mit) by using fluorescence Ca2+indicators, Fura-4F, and X-Rhod-1, respectively, and examined the protective effects of drugs on [Ca2+]cytand [Ca2+]mitoverloading by repeating 80K exposure. TND1128 (0.01, 0.1, and 1 mg/kg s.c.) mitigates the dynamics of both [Ca2+]cytand [Ca2+]mitin a dose-dependent manner. β-NMN (10, 30, and 100 mg/kg s.c.) also showed significant dose-dependent mitigating effects on [Ca2+]cyt, but the effect on the [Ca2+]mitdynamics was insignificant. We confirmed the mitochondria-activating potential of TND1128 in the present study. We expect TND1128 as a drug that rescues deteriorating neurons with aging or disease.