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Invited researcher Ilya Borisovich Bezprozvanniy
Contract number
11.G34.31.0056
Time span of the project
2011-2015

As of 30.01.2020

20
Number of staff members
54
scientific publications
3
Objects of intellectual property
General information

Name of the project: The role of calcium signaling in neurodegenerative diseases

Strategy for Scientific and Technological Development Priority Level: в


Goals and objectives

Research directions: Molecular and cellular medicine

Project objective: Research of molecular mechanisms of formation and development of neurodegenerative diseases, search for methods of treatment of disruption of work of neurons that lead to neurodegenerative diseases


The practical value of the study

  • We have found prototypes of medications against neurodegenerative diseases that normalize concentration of calcium in neurons. Research of potential medications against Alzheimer's disease have entered the pre-clinical stage.
  • We have determined a promising chemical compound for future development of a therapeutic agent against spinocerebellar ataxia type 2.
  • A method has been developed for controlling functional activity of nerve cells that allows to track single neurons both in cell cultures and whole animals.
  • Our researchers have found new mechanisms responsible for aging-related changes of calcium signaling in neurons of transgenic mice with illnesses modeling Huntington disease, Alzheimer's disease and spinocerebellar ataxia type 2.

Implemented results of research:

  • We have obtained a patent for our invention: «Application of piperazine derivatives for treatment of Alzheimer's disease and Alzheimer type dementia with disruption of intracellular calcium signaling».
  • Research of calcium signaling in neurons gives an opportunity to determine specific targets for creating new medications against neurodegenerative diseases. Subsequently, producing medications that are able to normalize calcium homeostasis of nerve cells attracts high interests from the world pharmaceutical industry.

Education and career development:

  • The Laboratory has become the base of the «Neurobiological engineering» masters program.
  • 1 doctoral dissertation, 5 candidate dissertations, 11 bachelors and masters dissertations have been defended.

Organizational and structural changes: The Laboratory has been completely integrated into educational structure of the Peter the Great Saint Petersburg Polytechnic University.

Collaborations:

  • B. P. Konstantinov Petersburg Nuclear Physics Institute (Russia): joint research and student exchanges
  • I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences (Russia), University of Texas Southwestern Medical Center in Dallas (USA): joint research and publications
  • I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences (Russia), Institute of Cytology of the Russian Academy of Sciences (Russia), Ataxion (USA), Teva (Israel), Garmoniya Ltd (Russia): joint research


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Sun S., Zhang H., Liu J., Popugaeva E., Xu N.-J., Feske S., White C.L., Bezprozvanny I.
Reduced Synaptic STIM2 Expression and Impaired Store-Operated Calcium Entry Cause Destabilization of Mature Spines in Mutant Presenilin Mice. Neuron 82(2): 79–93 (2014).
Popugaeva E., Pchitskaya E., Speshilova A., Zhang H., Vlasova O., Alexandrov S., Bezprozvanny I.
STIM2 Protects Hippocampal Mushroom Spines from Amyloid Synaptotoxicity. Journal of Molecular Neurodegeneration 10(1): 37 (2015).
Artamonov D.N., Korzhova V.V., Vlasova O.L., Bezprozvannyi I.B.
Optogenetic Approach to the Studies of Synaptic Transmission. Bulletin of Experimental Biology and Medicine 157(3): 404–407 (2014).
Popugaeva E., Chernyuk D., Zhang H., Postnikova T.Y., Pats K., Fedorova E., Poroikov V., Zaitsev A.V., Bezprozvanny I.
Derivatives of Piperazines as Potential Therapeutic Agents for Alzheimer's Disease. Molecular Pharmacology 95(4):337-348 (2019).
Popugaeva E., Pchitskaya E., Bezprozvanny I.
Dysregulation of Intracellular Calcium Signaling in Alzheimer's Disease. Antioxidants & Redox Signaling 29(12):1176-1188 (2018).
Egorova P.A., Gavrilova A.V., Bezprozvanny I.B.
In Vivo Analysis of the Climbing Fiber-Purkinje Cell Circuit in SCA2-58Q Transgenic Mouse Model. Cerebellum 17(5):590-600 (2018).
Egorova P.A., Bezprozvanny I.B.
Inositol 1,4,5-trisphosphate receptors and neurodegenerative disorders. FEBS Journal 285(19): 3547-3565 (2018).
Pchitskaya E., Kraskovskaya N., Chernyuk D., Popugaeva E., Zhang H., Vlasova O., Bezprozvanny I.
Stim2-Eb3 Association and Morphology of Dendritic Spines in Hippocampal Neurons. Scientific Reports 7(1):17625 (2018).
Pchitskaya E., Popugaeva E., Bezprozvanny I.
Calcium signaling and molecular mechanisms underlying neurodegenerative diseases. Cell Calcium 70:87-94 (2018).
Zhemkov V.A., Kulminskaya A.A., Bezprozvanny I.B., Kim M.
The 2.2-Angstrom resolution crystal structure of the carboxy-terminal region of ataxin-3. FEBS Open Bio 6(3):168-78 (2016).
Egorova P.A., Zakharova O.A., Vlasova O.L., Bezprozvanny I.B.
In vivo analysis of cerebellar Purkinje cell activity in SCA2 transgenic mouse model. Journal of Neurophysiology 115(6):2840-51 (2016).
Popugaeva E., Pchitskaya E., Speshilova A., Alexandrov S., Zhang H., Vlasova O., Bezprozvanny I.
STIM2 protects hippocampal mushroom spines from amyloid synaptotoxicity. Molecular Neurodegeneration 10: 37 (2015).
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