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Laboratory for Molecular Mechanisms of Neurodegeneration and Ageing

Contract number
14.Z50.31.0014
Time span of the project
2014-2018
Head of the laboratory

As of 01.11.2022

43
Number of staff members
64
scientific publications
3
Objects of intellectual property
General information

Name of the project: New approaches in research of regulation of aging and neurodegeneration processes in model organisms


Goals and objectives

Research directions: Identifying and characterizing new genes and metabolic paths that control aging and neurodegeneration

Project objective: Investigating molecular mechanisms of aging and neurodegeneration


The practical value of the study

Scientific results:

  • We have shown for the first time that it is not glucose itself but a product of its metabolism – glycogen – that is responsible for the reduction of the lifespan of nematodes. The role of the activity of AMP-activated protein kinase (AMPK) in the regulation of the lifespan of C.elegans.
  • Our researchers have demonstrated the geroprotective effect of the natural nucleotide AICAR that increases the mean lifespan of C.elegans and D.melanogaster by from 9 to 22 percent. A new model has been proposed that describes DNA reparation that is based on the age-related shift of RNA polymerase from the location of DNA damage with the participation of the protein factors UvrD and DksA and the ppGpp alarmone.
  • It has been shown that the recombinant human stress protein (HSP70), when chronically administered intranasally, positively affects cognitive abilities in old animals (mice). Chronically administering HSP70 both to old and young animals reliably improves the quality and increases their lifespan, and this effect is observed only in males.
  • We have demonstrated that when different lines of nematodes are used to conduct analysis of the amyloidogenic and toxic properties of isoAbeta(1-42) and pS8-Abeta(1-42), which are involved in the Alzheimer’s disease, in comparison with native Abeta(1-42), the studied isoforms  of beta-amyloid interact in a different manner with endogenous Abeta molecules and are able to either accelerate of decelerate the aggregation of nematodes in the organism – as a result, they can modulate the neurotoxic effects, thus changing the mean lifespan of nematodes. 

Implemented results of research: 

Three patents for inventions have been obtained: «A genetic structure for the expression of the functionally active human stress protein (HSP70) with mutated glycosylation site for  accumulation in eukaryotic expression systems», «A geroprotector for model animals», «The rHSP70  genetic structure for the expression of the principal human stress protein in dairy of transgenic animals». 

Education and career development:

  • One Doctor of Sciences and 7 Candidate of Sciences dissertations have been defended.
  • Internships: seven postgraduate students and young researchers from other organizations have completed internships at the Laboratory.
  • Lectures have been taught as part of the course «Molecular biology of the gene» for bachelor’s degree students of the Department of Molecular and Cell Biology of the Moscow Institute of Physics and Technology.
  • A school has been organized for young researchers with the topic «Redox regulation in biological systems».
  • An education program has been developed for the course «Molecular biology of the gene» for students of the Department Molecular and Cell Biology of the Moscow Institute of Physics and Technology..

Collaborations:

New York University School of Medicine (USA), National Institutes of Health (USA), Institute of Cell Biophysics of the Russian Academy of Sciences: joint research and publications .

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Popova А.А., Koksharova O.A., Lipasova V.A., Zaitseva J.V., Katkova-Zhukotskaya O.A., Eremina S.Iu., Mironov A.S., Chernin L.S., Khmel I.A.
Inhibitory and Toxic Effects of Volatiles Emitted by Strains of Pseudomonas and Serratia on Growth and Survival of Selected Microorganisms, Caenorhabditis elegans and Drosophila melanogaster. BioMed Research International Article ID 125704 (2014).
Venu K., Epshtein V., Bradley B., Proshkin S., Mironov A., Cashel M., Nudler E.
ppGpp Couples Transcription to DNA Repair in E.coli. Science 352 (6288): 993–996 (2016).
Gusarov I., Pani B., Gautier L., Smolentseva O., Eremina S., Shamovsky I., Katkova-Zhukotskaya O., Mironov A., Nudler E.
Glycogen Controls Caenorhabditis elegans Lifespan and Resistance to Oxidative Stress. Nature Communication 8: 15868 (2017).
Bobkova N.V., Evgen’ev M.В., Garbuz D.G., Kulikov A.M., Morozov A., Samokhin A., Velmeshev D., Medvinskaya N., Nesterova I., Pollock A., Nudler E.
Exogenous Hsp70 Delays Senescence and Improves Cognitive Function in Aging Mice. Proceedings of the National Academy of Sciences (USA) 112(52): 16006–16011 (2015).
Shilova V.Y., Zatsepina O.G., Garbuz D.G., Funikov S.Y., Zelentsova E.S., Schostak N.G., Kulikov A.M., Evgen’ev M.B.
Heat Shock Protein 70 from a Thermotolerant Diptera species Provides Higher Thermoresistance to Drosophila larvae than Correspondent Endogenous Gene. Insect Molecular Biology 27(1): 61–72 (2018).
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