Prospects for the Use of NF-кb Inhibitors to Stimulate the Functions of Regeneration-Competent Cells of Nerve Tissue and Neuroregeneration in Ethanol-Induced Neurodegeneration
G. N. Zyuz’kov, Larisa Stavrova, Larisa Arkad`evna Miroshnichenko, Tatyana Yur`evna Polykova, Е. В. Симанина, A Koeppen, G Zyuz'kov, L Miroshnichenko, T Polyakova, L Stavrova, E Simanina, V Zhdanov, K Zhang, H Wang, M Xu, J Frank, J Luo, Tateno, T Saito, J Brust, L Coleman, J He, J Lee, M Styner, F Crews, G Jordaan, R Emsley, K Nixon, G Zyuz'kov, V Zhdanov, E Udut, L Miroshnichenko, T Polyakova, L Stavrova, A Chaikovskii, E Simanina, M Minakova, V Udut, G Zyuz'kov, V Zhdanov, E Udut, L Miroshnichenko, E Simanina, T Polyakova, L Stavrova, V Udut, M Minakova, A Dygai, G Zyuz'kov, V Zhdanov, E Udut, L Miroshnichenko, T Polyakova, L Stavrova, V Udut, K Zhou, S Guo, S Tong, Q Sun, F Li, X Zhang, Y Qiao, G Liang, Y Li, O Sibon, P Dijkers, G Zyuz'kov, L Miroshnichenko, T Polyakova, L Stavrova, E Simanina, V Agafonov, E Udut, V Zhdanov, T Seki, C Kantzer, C Boutin, I Herzig, C Wittwer, S Rei, M Tiveron, J Drewes, T Rockel, S Ohlig, J Ninkovic, H Cremer, S Pennartz, M Jungblut, A Bosio, S Werneburg, H Fuchs, I Albers, H Burkhardt, V Gudi, T Skripuletz, M Stangel, R Gerardy-Schahn, H Hildebrandt, C Sousa, A Golebiewska
Abstract
The implementation of the concept of drug therapy of neurological disorders in chronic alcohol intoxication is, in some cases, unsuccessful. Promising is the search for new pharmacological targets among the intracellular signaling molecules of regenerating-competent cells. In the conditions of in vitro and in vivo modeling of ethanol-induced neurodegeneration, the role of NF-кВ in the realization of the growth potential of neural progenitors and the secretion of neurotrophins by glial elements was studied. The absence of participation of NF-кВ in the regulation of mitotic activity of neural SC (NSC) and of neuronal-committed progenitors (NCP) in their optimal living conditions and in the influence of ethanol in vitro is shown. At the same time, NF-кВ hinders the implementation of the NSC specialization process. The prolonged introduction of ethanol per os mice was accompanied by the appearance of an inhibitory value in NF-кВ in relation to the intensity of progenitors proliferation. The blockade of NF-кВ of NSC and NCP animals with neurodegeneration caused the progression of their cell cycle. The participation of NF-кВ in the secretory function of astrocytes and oligodendrogliocytes has been established. The inactivation of the nuclear transcription factor led to a decrease in their production of neurotrophins, including in the case of ethanol. At the same time, there were no changes from the microglia functioning.