An antioxidant specifically targeting mitochondria delays progression of Alzheimer's disease-like pathology.
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.
['Stefanova|Natalia A|NA|', 'Muraleva|Natalia A|NA|', 'Maksimova|Kseniya Yi|KY|', 'Rudnitskaya|Ekaterina A|EA|', 'Kiseleva|Elena|E|', 'Telegina|Darya V|DV|', 'Kolosova|Nataliya G|NG|']
D000544:Alzheimer Disease D016229:Amyloid beta-Peptides D000818:Animals D000975:Antioxidants D001921:Brain D004195:Disease Models, Animal D018450:Disease Progression D008928:Mitochondria D009474:Neurons D010446:Peptide Fragments D010766:Phosphorylation D010971:Plastoquinone D051381:Rats D017208:Rats, Wistar D016875:tau Proteins
mitochondria Alzheimer’s disease amyloid neurodegeneration synapse