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.
