摘要
背景:线粒体功能障碍被称为大脑衰老和阿尔茨海默病(AD)之间缺失的联系,阿尔茨海默病是世界范围内最常见的与年龄有关的痴呆类型。最先进和有前途的预防或减缓AD的方法是针对线粒体的治疗策略。 目的:线粒体靶向抗氧化剂SkQ1可以抑制AD体征的发展,但其在临床阶段AD的治疗潜力目前尚不清楚。 方法:利用模拟散发性AD主要特征的OXYS大鼠,评估SkQ1治疗19〜24个月对自发性和探索性活动的影响,磁共振成像(MRI)检测神经变性征象,淀粉样β蛋白Aβ)蛋白水平和海马神经元线粒体结构的影响。 结果:用SkQ1处理增加了OXYS和Wistar(对照)大鼠的行为活动。根据MRI,SkQ1仅在Wistar大鼠中减少了具有脱髓鞘的动物的百分比。同时,抗氧化剂还能降低两种大鼠海马组织中海马的Αβ1-40和Αβ1-42的蛋白水平,而不影响血清ββ的水平。 OXYS大鼠线粒体数目明显减少; SkQ1对此参数没有影响,但显着降低了两种大鼠品系线粒体的破坏性变化。结果,OXYS大鼠线粒体严重受损的比例下降,而Wistar大鼠线粒体完整线粒体比例上升。 结论:根据我们过去和现在的结果,SkQ1修复线粒体设备是一种有希望的抗AD的策略。
关键词: 阿尔茨海默病,线粒体,Aβ,SkQ1,神经变性,OXYS大鼠。
Current Alzheimer Research
Title:Antioxidant SkQ1 Alleviates Signs of Alzheimer’s Disease-like Pathology in Old OXYS Rats by Reversing Mitochondrial Deterioration
Volume: 14 Issue: 12
关键词: 阿尔茨海默病,线粒体,Aβ,SkQ1,神经变性,OXYS大鼠。
摘要: Background: 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.
Objective: Mitochondria-targeted antioxidant SkQ1 can suppress the development of AD signs, but its therapeutic potential in AD at clinical stages is currently unknown.
Method: 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.
Results: 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.
Conclusion: According to our past and present results, the repair of the mitochondrial apparatus by SkQ1 is a promising strategy against AD.
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Antioxidant SkQ1 Alleviates Signs of Alzheimer’s Disease-like Pathology in Old OXYS Rats by Reversing Mitochondrial Deterioration, Current Alzheimer Research 2017; 14 (12) . https://dx.doi.org/10.2174/1567205014666170621111033
DOI https://dx.doi.org/10.2174/1567205014666170621111033 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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