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Contract number
075-15-2019-1877, 075-15-2022-1095
Time span of the project
2019-2023

As of 01.11.2022

35
Number of staff members
30
scientific publications
3
Objects of intellectual property
General information

Name of the project: Study of the mechanisms of mitochondrial dysfunction in cell models in neurodegenerative diseases


Goals and objectives

Project objective:

1. Determining how toxins or abnormal proteins encoded by mutated gene cause changes in mitochondrial function.

2. Developing a strategy to protect neurons in context neurodegenerative diseases based on correction of functions of mitochondria.

3. Developing an in vivo method of detecting pathological changes in mitochondrial metabolism during neurodegenerative diseases.

The practical value of the study

Scientific results:

  • We have determined the selectivity of lesions of regions of the brain in neurodegeneration and the relation with the difference in processes of education and energy consumption. [Vinokurov AY, Stelmashuk OA, Ukolova PA, Zherebtsov EA, Abramov AY. Brain region specificity in reactive oxygen species production and maintenance of redox balance. //  Free Radic Biol Med. 2021;174:195-201. doi:10.1016/j.freeradbiomed.2021.08.014; Baev AY, Vinokurov AY, Novikova IN, Dremin VV, Potapova EV, Abramov AY. Interaction of Mitochondrial Calcium and ROS in Neurodegeneration. // Cells. 2022;11(4). doi:10.3390/cells11040706; Cheng X, Vinokurov AY, Zherebtsov EA, et al. Variability of mitochondrial energy balance across brain regions. // J Neurochem. 2021;157(4):1234-1243. doi:10.1111/jnc.15239].
  • On the basis of a study of the fundamental mechanisms of neurodegenerative diseases, we have refined the methodological foundations of new strategies and methods of cell protection. [Fedotova EI, Dolgacheva LP, Abramov AY, Berezhnov AV. Lactate and Pyruvate Activate Autophagy and Mitophagy that Protect Cells in Toxic Model of Parkinson’s Disease. //  Mol Neurobiol. 2022;59(1):177-190. doi:10.1007/s12035-021-02583-8; Shevtsova EF, Angelova PR, Stelmashchuk OA, et al. Pharmacological sequestration of mitochondrial calcium uptake protects against dementia and β-amyloid neurotoxicity. // Sci Rep. 2022;12(1). doi:10.1038/s41598-022-16817-9].
  • As part of the study of methods of the production of singlet oxygen during irradiation by laser at a wavelength of 1267 nm, we have determined the protective and restorative action on altered mitochondrial metabolism in neuronal cells with mutations related to different hereditary forms. [Olga A. Stel’mashchuk, Irina N. Novikova, Yelena V. Potapova, Viktor V. Dryomin, Andrey Yu. Abramov, Yevgeniy A. Zherebtsov. Andrey V. Dunayev, «Method for protection neurons in neurodegenerative diseases and  appaatus for implementation thereof» (decision on the granting of a patent of 03 October 2022)].

  • We have accumulated data on the overwhelming influence of singlet oxygen on pathological cells of the B16 line and the absence of negative impact on healthy fibroblasts. [Irina N. Novikova, Yelena V. Potapova, Viktor V. Dryomin, Andrey V. Dunayev, Andrey Yu. Abramov. Laser-induced singlet oxygen selectively triggers oscillatory mitochondrial permeability transition and apoptosis in melanoma cell lines. // Life Sci. 2022;304. doi:10.1016/j.lfs.2022.120720]. 

Implementation of research results

  • The developed methods of the assessment of the metabolism of mitochondria and the redox-balance of cells are actively used in the execution of commercial agreements for the analysis of biologically active substances in the Laboratory.

  • Methodological developments in the imaging of intracellular processes in biological tissues of various origins are used in laboratory case studies as well as the organization of project activities of students of the Orel State University. 

Education and retraining of personnel
  • We have developed the basic professional education program (for highly qualified professionals training) in the direction 06.06.01 Biological sciences, major (profile) - Physiology (Orel State University, 2020).
  • As part of teaching activity at the university we are implementing disciplines for postgraduate students (direction 06.06.01 Biological sciences, major (profile) - Physiology): «Pathophysiological basics of neurodegenerative diseases» and «Human and animal physiology» (2020-2022).
  • We have developed additional education programs «Methods of working with cell cultures» (2021), «Confocal laser scanning microscopy in the practice of preclinical testing of pharmaceuticals» (2021), «Foundations of in vitro and ex vivo cell research» (2022).

Collaborations:

Institute of Neurology of University College London, Aston University (United Kingdom), University of Oulu (Finland), Institute of Cell Biophysics of the Russian Academy of Sciences, Center for the collective use of scientific equipment «Genome editing» of the Institute of Gene Biology of the Russian Academy of Sciences, Institute of Physiologically Active Compounds of Russian Academy of Sciences, Belgorod State University, Orel Regional Clinical Hospital, Budgetary Healthcare Institution of the Orel Region «Research & Clinical Multifunctional Center of Medical Care for Mothers and Children»», Family Clinic Network (Russia): joint research. 

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i.n. novikova, e.v. potapova,v.v. dremin, a.d. dunaev, a.y. abramov
Laser-induced singlet oxygen selectively triggers oscillatory mitochondrial permeability transition and apoptosis in melanoma cell lines, Life Sciences, 2022, 304, 120720.
e.f. shevtsova, p.r. angelova, o.a. stelmashchuk, n. esteras, n.a. vasil’eva, a.v. maltsev, p.n. shevtsov, a.v. shaposhnikov, v.p. fisenko, s.o. bachurin, a.y. abramov
Pharmacological sequestration of mitochondrial calcium uptake protects against dementia and β-amyloid neurotoxicity, Scientific Reports, 2022, 12(1), 1-17.
a.y. baev, a.y. vinokurov, i.n. novikova, v.v. dremin, e.v. potapova, a.y. abramov
Interaction of Mitochondrial Calcium and ROS, Cells, 2022, 11(4), 706.
komilova, n. r., angelova, p. r., berezhnov, a. v., stelmashchuk, o. a., mirkhodjaev, u. z., houlden, h., gourine a.v., esteras n. & abramov, a. y.
Metabolically induced intracellular pH changes activate mitophagy, autophagy, and cell protection in familial forms of Parkinson's disease// The FEBS Journal, 2021, 289(3), 699-711
vinokurov, a. y., stelmashuk, o. a., ukolova, p. a., zherebtsov, e. a., & abramov, a. y.
Brain region specificity in reactive oxygen species production and maintenance of redox balance// Free Radical Biology and Medicine, 2021, 174, 195-201.
cheng x., vinokurov a., zherebtsov e., stelmashchuk o., angelova p., esteras n., abramov a.
Variability of mitochondrial energy balance across brain regions // Journal of Neurochemistry, 2020
novikova i., manole a., zherebtsov e., stavtsev d., vukolova m., dunaev a., angelova p., abramov a.
Adrenaline induces calcium signal in astrocytes and vasoconstriction via activation of monoamine oxidase // Free Radical Biology and Medicine, 2020, 159, p. 15 - 22
abramov a., potapova e., dremin v., dunaev a.
Interaction of Oxidative Stress and Misfolded Proteins in the Mechanism of Neurodegeneration, Life, 2020, 10 101
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