The mitochondria-targeted antioxidant MitoQ extends lifespan and improves healthspan of a transgenic Caenorhabditis elegans model of Alzheimer disease
The mitochondria-targeted antioxidant MitoQ extends lifespan and improves healthspan of a transgenic Caenorhabditis elegans model of Alzheimer disease
复制标题
DOI：
10.1016/j.freeradbiomed.2014.03.003
复制
发表时间：
2014-06-01
影响因子：
7.4
通讯作者：
Halliwell, Barry
中科院分区：
文献类型：
--
作者：
Ng, Li Fang;Gruber, Jan;Halliwell, Barry
β-淀粉样蛋白 (Aβ) 诱导的毒性和氧化应激被认为在阿尔茨海默病 (AD) 的致病机制中发挥着关键作用。我们研究了线粒体靶向抗氧化剂 MitoQ 在过度表达人类 Aβ 的秀丽隐杆线虫模型中抵御 Aβ 诱导的毒性和氧化应激的体内能力。电子传递链 (ETC) 酶活性受损和线粒体功能障碍是 AD 的早期特征。我们发现 MitoQ 可以延长寿命，延迟 Aβ 诱导的麻痹，改善线粒体脂质心磷脂的消耗，并保护 ETC 的复合物 IV 和 I。尽管 MitoQ 对寿命、健康寿命和 ETC 功能具有保护作用，但我们发现 MitoQ 不会降低 DCFDA 荧光、蛋白质羰基水平或调节稳态 ATP 水平或耗氧率。此外，MitoQ 不会减轻线粒体 DNA (mtDNA) 氧化损伤。与其设计一致，MitoQ 的保护作用似乎专门针对线粒体膜，我们的研究结果表明 MitoQ 可能对 Aβ 和氧化应激相关的神经退行性疾病（尤其是 AD）具有治疗潜力。 (C) 2014 年作者。由爱思唯尔公司出版
beta-Amyloid (A beta)-induced toxicity and oxidative stress have been postulated to play critical roles in the pathogenic mechanism of Alzheimer disease (AD). We investigated the in vivo ability of a mitochondria-targeted antioxidant, MitoQ to protect against A beta-induced toxicity and oxidative stress in a Caenorhabditis elegans model overexpressing human A beta. Impairment of electron transport chain (ETC) enzymatic activity and mitochondrial dysfunction are early features of AD. We show that MitoQ extends lifespan, delays A beta-induced paralysis, ameliorates depletion of the mitochondrial lipid cardiolipin, and protects complexes IV and I of the ETC. Despite its protective effects on lifespan, healthspan, and ETC function, we find that MitoQ does not reduce DCFDA fluorescence, protein carbonyl levels or modulate steadystate ATP levels or oxygen consumption rate. Moreover, MitoQ does not attenuate mitochondrial DNA (mtDNA) oxidative damage. In agreement with its design, the protective effects of MitoQ appear to be targeted specifically to the mitochondrial membrane and our findings suggest that MitoQ may have therapeutic potential for A beta- and oxidative stress-associated neurodegenerative disorders, particularly AD. (C) 2014 The Authors. Published by Elsevier Inc.