Research Paper Volume 8, Issue 11 pp 2713—2733

An antioxidant specifically targeting mitochondria delays progression of Alzheimer’s disease-like pathology

Natalia A. Stefanova1, , Natalia A. Muraleva1, , Kseniya Yi. Maksimova2, , Ekaterina A. Rudnitskaya1, , Elena Kiseleva1, , Darya V. Telegina1, , Nataliya G. Kolosova1,3, ,

  • 1 Institute of Cytology and Genetics SB RAS, 630090, Novosibirsk, Russia
  • 2 Siberian State Medical University, 634055, Tomsk, Russia
  • 3 Novosibirsk State University, 630090, Novosibirsk, Russia

Received: June 14, 2016       Accepted: September 18, 2016       Published: October 6, 2016      

https://doi.org/10.18632/aging.101054
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Abstract

Mitochondrial aberrations are observed in human Alzheimer’s disease (AD) and in medical conditions that increase the risk of this disorder, suggesting that mitochondrial dysfunction may contribute to pathophysiology of AD. Here, using OXYS rats that simulate key characteristics of sporadic AD, we set out to determine the role of mitochondria in the pathophysiology of this disorder. OXYS rats were treated with a mitochondria-targeted antioxidant SkQ1 from age 12 to 18 months, that is, during active progression of AD-like pathology in these animals. Dietary supplementation with SkQ1 caused this compound to accumulate in various brain regions, and it was localized mostly to neuronal mitochondria. Via improvement of structural and functional state of mitochondria, treatment with SkQ1 alleviated the structural neurodegenerative alterations, prevented the neuronal loss and synaptic damage, increased the levels of synaptic proteins, enhanced neurotrophic supply, and decreased amyloid-β1-42 protein levels and tau hyperphosphorylation in the hippocampus of OXYS rats, resulting in improvement of the learning ability and memory. Collectively, these data support that mitochondrial dysfunction may play a key role in the pathophysiology of AD and that therapies with target mitochondria are potent to normalize a wide range of cellular signaling processes and therefore slow the progression of AD.

Abbreviations

APP: amyloid precursor protein; SkQ1: plastoquinonyl-decyltriphenylphosphonium.