Caprylic triglyceride as a novel therapeutic approach to effectively improve the performance and attenuate the symptoms due to the motor neuron loss in ALS disease.
Caprylic triglyceride as a novel therapeutic approach to effectively improve the performance and attenuate the symptoms due to the motor neuron loss in ALS disease.
复制标题
DOI：
10.1371/journal.pone.0049191
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Pasinetti GM
中科院分区：
文献类型：
--
作者：
Zhao W;Varghese M;Vempati P;Dzhun A;Cheng A;Wang J;Lange D;Bilski A;Faravelli I;Pasinetti GM
肌萎缩侧索硬化症（ALS）是一种运动神经元的神经退行性疾病，其导致进行性肌肉无力、瘫痪，最终死亡。ALS患者患有虚弱，他们的进行性虚弱对生活质量产生负面影响，限制了他们的日常活动。他们损害了与ALS脊髓中线粒体电子传递链酶活性降低相关的能量平衡，这表明改善线粒体功能可能是ALS的治疗方法。当喂食生酮饮食时，G93 A ALS小鼠显示出血清酮的显著增加以及虚弱进展的显著减慢和死亡率的降低。在这项研究中，我们用辛酸甘油三酯治疗SOD 1-G93 A小鼠，辛酸甘油三酯是一种中链甘油三酯，代谢为酮体，可以作为神经元代谢的替代能量底物。用辛酸甘油三酯治疗减弱了SOD 1-G93 A转基因动物中虚弱的进展并保护了脊髓运动神经元的损失，显著改善了它们的表现，尽管关于ALS转基因动物的存活没有显著益处。我们发现，辛酸甘油三酯显着促进线粒体耗氧率在体内。我们的研究结果表明，辛酸甘油三酯通过恢复SOD 1-G93 A ALS小鼠的能量代谢，特别是在疾病的明显阶段，减轻ALS型运动障碍。这些数据表明使用辛酸作为一种易于管理的治疗方法的可行性，对ALS患者的生活质量有很大的影响。
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and finally death. ALS patients suffer from asthenia and their progressive weakness negatively impacts quality of life, limiting their daily activities. They have impaired energy balance linked to lower activity of mitochondrial electron transport chain enzymes in ALS spinal cord, suggesting that improving mitochondrial function may present a therapeutic approach for ALS. When fed a ketogenic diet, the G93A ALS mouse shows a significant increase in serum ketones as well as a significantly slower progression of weakness and lower mortality rate. In this study, we treated SOD1-G93A mice with caprylic triglyceride, a medium chain triglyceride that is metabolized into ketone bodies and can serve as an alternate energy substrate for neuronal metabolism. Treatment with caprylic triglyceride attenuated progression of weakness and protected spinal cord motor neuron loss in SOD1-G93A transgenic animals, significantly improving their performance even though there was no significant benefit regarding the survival of the ALS transgenic animals. We found that caprylic triglyceride significantly promoted the mitochondrial oxygen consumption rate in vivo. Our results demonstrated that caprylic triglyceride alleviates ALS-type motor impairment through restoration of energy metabolism in SOD1-G93A ALS mice, especially during the overt stage of the disease. These data indicate the feasibility of using caprylic acid as an easily administered treatment with a high impact on the quality of life of ALS patients.
登录
查看更多内容
影响因子：
4.5
作者：
Henderson, Samuel T.;Vogel, Janet L.;Costantini, Lauren C.
通讯作者：
Costantini, Lauren C.
影响因子：
1.9
作者：
Hu, Zhi-Gang;Wang, Han-Dong;Yin, Hong-Xia
通讯作者：
Yin, Hong-Xia
影响因子：
7.1
作者：
BACH, AC;BABAYAN, VK
通讯作者：
BABAYAN, VK
影响因子：
2.9
作者：
Cheng, Baohua;Yang, Xinxin;Liu, Shuwei
通讯作者：
Liu, Shuwei
影响因子：
5.5
作者：
Douglas, Robert M.;Ryu, Julie;Ali, Sameh S.
通讯作者：
Ali, Sameh S.