Antioxidant SkQ1 Alleviates Signs of Alzheimer’s Disease-like Pathology in Old OXYS Rats by Reversing Mitochondrial Deterioration

Author(s): Nataliya G. Kolosova*, Mikhail A. Tyumentsev, Natalia A. Muraleva, Elena Kiseleva, Anton O. Vitovtov, Natalia A. Stefanova*.

Journal Name: Current Alzheimer Research

Volume 14 , Issue 12 , 2017

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Abstract:

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.

Keywords: Alzheimer's disease, mitochondria, Aβ, SkQ1, neurodegeneration, OXYS rats.

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Article Details

VOLUME: 14
ISSUE: 12
Year: 2017
Page: [1283 - 1292]
Pages: 10
DOI: 10.2174/1567205014666170621111033
Price: $58

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