Kolosova Nataliya G, Tyumentsev Mikhail A, Muraleva Natalia A, Kiseleva Elena, Vitovtov Anton O, Stefanova Natalia A
Institute of Cytology and Genetics SB RAS, Prospekt Lavrentyeva 10; Novosibirsk 630090. Russian Federation.
Institute of Cytology and Genetics SB RAS, Novosibirsk 630090. Russian Federation.
Curr Alzheimer Res. 2017;14(12):1283-1292. doi: 10.2174/1567205014666170621111033.
Mitochondrial dysfunction is called the missing link between brain aging and Alzheimer's disease (AD), the most common type of age-related dementia worldwide. Among the most advanced and promising of approaches to prevention or slowing of AD are therapeutic strategies targeting mitochondria.
Mitochondria-targeted antioxidant SkQ1 can suppress the development of AD signs, but its therapeutic potential in AD at clinical stages is currently unknown.
Using OXYS rats that simulate key characteristics of sporadic AD, we evaluated effects of SkQ1 treatment from the age of 19 to 24 months on the locomotor and exploratory activities, signs of neurodegeneration detectable by magnetic resonance imaging (MRI), amyloid-β (Aβ) protein levels in the hippocampus and serum, and structure of the mitochondrial apparatus in hippocampal neurons.
Treatment with SkQ1 increased behavioral activity in OXYS and Wistar (control) rats. According to MRI, SkQ1 decreased the percentage of animals with demyelination only among Wistar rats. At the same time, the antioxidant reduced hippocampal Аβ1-40 and Аβ1-42 protein levels in both rat strains and did not affect serum Аβ levels. The number of mitochondria was significantly lower in OXYS rats; SkQ1 had no effect on this parameter but significantly reduced the destructive changes in mitochondria of both rat strains. As a result, in OXYS rats, the proportion of severely damaged mitochondria decreased, whereas in Wistar rats, the proportion of intact mitochondria increased.
According to our past and present results, the repair of the mitochondrial apparatus by SkQ1 is a promising strategy against AD.
线粒体功能障碍被认为是大脑衰老与阿尔茨海默病（AD）之间缺失的环节，AD是全球最常见的与年龄相关的痴呆类型。在预防或延缓AD的最先进且最有前景的方法中，针对线粒体的治疗策略备受关注。
线粒体靶向抗氧化剂SkQ1可抑制AD症状的发展，但其在AD临床阶段的治疗潜力目前尚不清楚。
我们使用模拟散发性AD关键特征的OXYS大鼠，评估了从19月龄至24月龄给予SkQ1治疗对其运动和探索活动、磁共振成像（MRI）可检测到的神经退行性变迹象、海马体和血清中淀粉样β蛋白（Aβ）水平以及海马神经元线粒体结构的影响。
SkQ1治疗增加了OXYS大鼠和Wistar（对照）大鼠的行为活动。根据MRI结果，SkQ1仅降低了Wistar大鼠中脱髓鞘动物的比例。同时，该抗氧化剂降低了两种大鼠品系海马体中Aβ1-40和Aβ1-42蛋白水平，且不影响血清Aβ水平。OXYS大鼠的线粒体数量显著减少；SkQ1对该参数无影响，但显著减少了两种大鼠品系线粒体的破坏变化。结果，在OXYS大鼠中，严重受损线粒体的比例降低，而在Wistar大鼠中，完整线粒体的比例增加。
根据我们过去和现在的研究结果，SkQ1修复线粒体结构是一种有前景的抗AD策略。
