Белогурова-Овчинникова Оксана Юрьевна

Кандидат биологических наук


Научный сотрудник (Отдел «Учебно-научный центр»)

Тел.: +7 (910) 4394341

Эл. почта: ovchox@gmail.com

Образование

Период обученияСтрана, городУчебное заведениеДополнительная информация
2002–2007 Москва, Россия Московский государственный университет им. М.В. Ломоносова Красный диплом
2007–2011 Цюрих, Швейцария Швейцарский высший технологический институт Ph.D. диплом

Избранные публикации

  1. Huber M., Ovchinnikova O.Y., Schütz A.K., Glockshuber R., Meier B.H., Böckmann A. (2015). Solid-state NMR sequential assignment of Osaka-mutant amyloid-beta (Aβ1-40 E22Δ) fibrils. Biomol NMR Assign 9 (1), 7–14 [+]

    Alzheimer's disease (AD) is the most common form of dementia. Aggregation of amyloid β (Aβ), a peptide of 39-43 residues length, into insoluble fibrils is considered to initiate the disease. Determination of the molecular structure of Aβ fibrils is technically challenging and is a significant goal in AD research that may lead to design of effective therapeutical inhibitors of Aβ aggregation. Here, we present chemical-shift assignments for fibrils formed by highly pure recombinant Aβ1-40 with the Osaka E22Δ mutation that is found in familial AD. We show that that all regions of the peptide are rigid, including the N-terminal part often believed to be flexible in Aβ wt.

    ID:1339
  2. Schütz A.K., Vagt T., Huber M., Ovchinnikova O.Y., Cadalbert R., Wall J., Güntert P., Böckmann A., Glockshuber R., Meier B.H. (2015). Atomic-resolution three-dimensional structure of amyloid β fibrils bearing the Osaka mutation. Angew. Chem. Int. Ed. Engl. 54 (1), 331–5 [+]

    Despite its central importance for understanding the molecular basis of Alzheimer's disease (AD), high-resolution structural information on amyloid β-peptide (Aβ) fibrils, which are intimately linked with AD, is scarce. We report an atomic-resolution fibril structure of the Aβ1-40 peptide with the Osaka mutation (E22Δ), associated with early-onset AD. The structure, which differs substantially from all previously proposed models, is based on a large number of unambiguous intra- and intermolecular solid-state NMR distance restraints.

    ID:1336
  3. Spirig T., Ovchinnikova O., Vagt T., Glockshuber R. (2014). Direct evidence for self-propagation of different amyloid-β fibril conformations. Neurodegener Dis 14 (3), 151–9 [+]

    Amyloid fibrils formed by amyloid-β (Aβ) peptides are associated with Alzheimer's disease and can occur in a range of distinct morphologies that are not uniquely determined by the Aβ sequence. Whether distinct conformations of Aβ fibrils can be stably propagated over multiple cycles of seeding and fibril growth has not been established experimentally.

    ID:1337
  4. Ovchinnikova O.Y., Finder V.H., Vodopivec I., Nitsch R.M., Glockshuber R. (2011). The Osaka FAD mutation E22Δ leads to the formation of a previously unknown type of amyloid β fibrils and modulates Aβ neurotoxicity. J. Mol. Biol. 408 (4), 780–91 [+]

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cerebral deposition of amyloid fibrils formed by the amyloid β (Aβ) peptide. Aβ has a length of 39-43 amino acid residues; the predominant Aβ isoforms are Aβ1-40 and Aβ1-42. While the majority of AD cases occur spontaneously, a subset of early-onset familial AD cases is caused by mutations in the genes encoding the Aβ precursor protein or presenilin 1/presenilin 2. Recently, a deletion of glutamic acid at position 22 within the Aβ sequence (E22Δ) was identified in Japanese patients with familial dementia, but the aggregation properties of the deletion variant of Aβ are not well understood. We investigated the aggregation characteristics and neurotoxicity of recombinantly expressed Aβ isoforms 1-40 and 1-42 with and without the E22Δ mutation. We show that the E22Δ mutation strongly accelerates the fibril formation of Aβ1-42 E22Δ compared to Aβ1-42 wild type (wt). In addition, we demonstrate that fibrils of Aβ1-40 E22Δ form a unique quaternary structure characterized by a strong tendency to form fibrillar bundles and a strongly increased thioflavin T binding capacity. Aβ1-40 E22Δ was neurotoxic in rat primary neuron cultures as compared to nontoxic Aβ1-40 wt. Aβ1-42 E22Δ was less toxic than Aβ1-42 wt, but it significantly decreased neurite outgrowth per cell in neuronal primary cultures. Because Aβ1-40 is the major Aβ form in vivo, the gain of toxic function caused by the E22 deletion may explain the development of familial AD in mutation carriers.

    ID:1338