title: An antioxidant specifically targeting mitochondria delays progression of Alzheimer's disease-like pathology.
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.
authors.affiliation: Institute of Cytology and Genetics SB RAS, 630090, Novosibirsk, Russia.
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Stefanova
authors.affiliation: Institute of Cytology and Genetics SB RAS, 630090, Novosibirsk, Russia.
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Muraleva
authors.affiliation: Siberian State Medical University, 634055, Tomsk, Russia.
authors.forename: Kseniya Yi
authors.initials: KY
authors.lastname: Maksimova
authors.affiliation: Institute of Cytology and Genetics SB RAS, 630090, Novosibirsk, Russia.
authors.forename: Ekaterina A
authors.initials: EA
authors.lastname: Rudnitskaya
authors.affiliation: Institute of Cytology and Genetics SB RAS, 630090, Novosibirsk, Russia.
authors.forename: Elena
authors.initials: E
authors.lastname: Kiseleva
authors.affiliation: Institute of Cytology and Genetics SB RAS, 630090, Novosibirsk, Russia.
authors.forename: Darya V
authors.initials: DV
authors.lastname: Telegina
authors.affiliation: Institute of Cytology and Genetics SB RAS, 630090, Novosibirsk, Russia.|Novosibirsk State University, 630090, Novosibirsk, Russia.
authors.forename: Nataliya G
authors.initials: NG
authors.lastname: Kolosova
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010971:Plastoquinone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D016875:tau Proteins / Q000378:metabolism
chemical_list: C532038:10-(6'-plastoquinonyl)decyltriphenylphosphonium; D016229:Amyloid beta-Peptides; D000975:Antioxidants; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D010971:Plastoquinone
keywords: Alzheimer’s disease; amyloid; mitochondria; neurodegeneration; synapse