We studied the role of NF-κB-, cAMP/PKA-, JAKs/STAT3-, ERK1/2-, p38-, JNK- and p53- mediated signaling pathways in the realization of the growth potential of neural stem cells and committed neuronal progenitors under in vitro conditions. The method of pharmacological blockade with selective inhibitors of individual signaling molecules revealed some principal differences in their role in the determination of the proliferation and differentiation status of progenitor cells of different classes. Analysis of the peculiarities of intracellular signaling in cells and comparison of the role of its individual elements attest to the prospects of developing new drugs with neuroregenerative activity based on STAT3 inhibitors or JNK activators. These modulations of activity of signaling molecules can stimulate the realization of the growth potential of committed neuronal progenitors and neutral stem cells, respectively. The blockade of STAT3 and an increase in the content of phosphorylated forms of JNK had no “negative” effects on the functioning of multipotent neural stem cells and committed neuronal progenitors, respectively.
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Zyuz’kov GN, Miroshnichenko LA, Polyakova TY, Zhdanov VV, Simanina EV, Stavrova LA. The Role of NF-κВ in the Realization of Functions of Various Types of Regeneration-Competent Cells of the Nervous Tissue in Ethanol-Induced Neurodegeneration. Bull. Exp. Biol. Med. 2020;169(6):759-764. doi: https://doi.org/10.1007/s10517-020-04973-9
Zyuz’kov GN, Miroshnichenko LA, Polyakova TY, Stavrova LA, Simanina EV, Zhdanov VV, Chaikovskii AV. Peculiarities of the Involvement of MAPKS ERK1/2 and р38 in the Implementation of the Functions of Neural Stem Cells and Neuronal Committed Precursors in Ethanol-Induced Neurodegeneration. Bull. Exp. Biol. Med. 2020;169(5):609-613. doi: https://doi.org/10.1007/s10517-020-04938-y
Fogarty CE, Bergmann A. Killers creating new life: caspases drive apoptosis-induced proliferation in tissue repair and disease. Cell Death Differ. 2017;24(8):1390-1400.
Jauregui E, Du L, Gleason C, Poovaiah BW. Autophosphorylation of calcium/calmodulin-dependent protein kinase (CCaMK) at S343 or S344 generates an intramolecular interaction blocking the CaM-binding. Plant. Signal Behav. 2017;12(7):e1343779. doi: https://doi.org/10.1080/15592324.2017.1343779
Jellinger KA. Neuropathology and pathogenesis of extrapyramidal movement disorders: a critical update. II. Hyperkinetic disorders. J. Neural Transm. (Vienna). 2019;126(8):997-1027.
Karakostis K, Fåhraeus R. Shaping the regulation of the p53 mRNA tumour suppressor: the co-evolution of genetic signatures. BMC Cancer. 2019;19(1):915. doi: https://doi.org/10.1186/s12885-019-6118-y
Mavers M, Ruderman EM, Perlman H. Intracellular signal pathways: potential for therapies. Curr. Rheumatol. Rep. 2009;11(5):378-385.
Neal M, Richardson JR. Epigenetic regulation of astrocyte function in neuroinflammation and neurodegeneration. Biochim. Biophys. Acta Mol. Basis Dis. 2018;1864(2):432-443.
Seki T. Expression patterns of immature neuronal markers PSA-NCAM, CRMP-4 and NeuroD in the hippocampus of young adult and aged rodents. J. Neurosci. Res. 2002;70(3):327-334.
Zyuz’kov GN, Miroshnichenko LA, Udut EV, Chaikovskii AV, Polyakova TY, Simanina EV, Stavrova LA, Agafonov VI, Zhdanov VV. Functional state of various types of regenerationcompetent cells in the nervous tissue in ethanol-induced neurodegeneration. Bull. Exp. Biol. Med;166 (3):317-320.
Zyuz’kov GN, Stavrova LA, Miroshnichenko LA, Polyakova TYu, Simanina EV. Prospects for the use of NF-κB inhibitors to stimulate the functions of regeneration-competent cells of nerve tissue and neuroregeneration in ethanol-induced neurodegeneration. Biointerface Res. Appl. Chem. 2021;11(1):8065-8074. https://doi.org/10.33263/BRIAC111.80658074
Zyuz’kov GN, Suslov NI, Miroshnichenko LA, Simanina EV, Polykova TY, Stavrova LA, Zhdanov VV, Minakova MY, Udut EV, Udut VV. Halogenated (Cl-ion) songorine is a new original agonist of fibroblast growth factor receptors of committed neuronal progenitors possessing neuroregenerative effect after cerebral ischemia and hypoxia in experimental animals. Biointerface Res. Appl. Chem. 2019;9(5):4317-4326.
Zyuz’kov GN, Udut EV, Miroshnichenko LA, Polyakova TY, Simanina EV, Stavrova LA, Chaikovskii AV, Agafonov VI, Borodulina EV, Timofeev MS, Zyuz’kova YN, Danilets MG, Zhdanov VV, Udut VV. Particular role of JAK/STAT3 signaling in functional control of mesenchymal progenitor cells. Bull. Exp. Biol. Med. 2018;164(3):316-319.
Zyuz’kov GN, Zhdanov VV, Udut EV, Miroshnichenko LA, Polyakova TY, Stavrova LA, Chaikovskii AV, Simanina EV, Minakova MY, Udut VV. Peculiarities of intracellular signal transduction in the regulation of functions of mesenchymal, neural, and hematopoietic progenitor cells. Bull. Exp. Biol. Med. 2019;167(2):201-206.
Zyuz’kov GN, Zhdanov VV, Udut EV, Miroshnichenko LA, Polyakova TY, Stavrova LA, Udut VV. Strategy of pharmacological regulation of intracellular signal transduction in regeneration-competent cells. Bull. Exp. Biol. Med. 2019;166(4):448-455.
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Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 4, pp. 231-236, December, 2020
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Zyuz’kov, G.N., Miroshnichenko, L.A., Polyakova, T.Y. et al. Specific Features of Intracellular Signal Transduction in the Regulation of Functions of Neural Stem Cells and Committed Neuronal Progenitors. Bull Exp Biol Med 170, 522–527 (2021). https://doi.org/10.1007/s10517-021-05100-y
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DOI: https://doi.org/10.1007/s10517-021-05100-y