Intracellular signaling molecules of nerve tissue progenitors as pharmacological targets for treatment of ethanol-induced neurodegeneration
© 2021 Walter de Gruyter GmbH, Berlin/Boston..
OBJECTIVES: The development of approaches to the treatment of neurodegenerative diseases caused by alcohol abuse by targeted pharmacological regulation of intracellular signaling transduction of progenitor cells of nerve tissue is promising. We studied peculiarities of participation of NF-кB-, сАМР/РКА-, JAKs/STAT3-, ERK1/2-, p38-pathways in the regulation of neural stem cells (NSC) and neuronal-committed progenitors (NCP) in the simulation of ethanol-induced neurodegeneration in vitro and in vivo.
METHODS: In vitro, the role of signaling molecules (NF-кB, сАМР, РКА, JAKs, STAT3, ERK1/2, p38) in realizing the growth potential of neural stem cells (NSC) and neuronal-committed progenitors (NCP) in ethanol-induced neurodegeneration modeled in vitro and in vivo was studied. To do this, the method of the pharmacological blockade with the use of selective inhibitors of individual signaling molecules was used.
RESULTS: Several of fundamental differences in the role of certain intracellular signaling molecules (SM) in proliferation and specialization of NSC and NCP have been revealed. It has been shown that the effect of ethanol on progenitors is accompanied by the formation of a qualitatively new pattern of signaling pathways. Data have been obtained on the possibility of stimulation of nerve tissue regeneration in ethanol-induced neurodegeneration by NF-кB and STAT3 inhibitors. It has been found that the blockage of these SM stimulates NSC and NCP in conditions of ethanol intoxication and does not have a «negative» effect on the realization of the growth potential of intact progenitors (which will appear de novo during therapy).
CONCLUSIONS: The results may serve as a basis for the development of fundamentally new drugs to the treatment of alcoholic encephalopathy and other diseases of the central nervous system associated with alcohol abuse.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:33 |
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| Enthalten in: |
Journal of basic and clinical physiology and pharmacology - 33(2021), 3 vom: 08. Feb., Seite 305-315 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zyuz'kov, Gleb Nikolaevich [VerfasserIn] |
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| Links: |
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| Themen: |
3K9958V90M |
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| Anmerkungen: |
Date Completed 24.05.2022 Date Revised 24.05.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1515/jbcpp-2020-0317 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Zyuz'kov, Gleb Nikolaevich |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Intracellular signaling molecules of nerve tissue progenitors as pharmacological targets for treatment of ethanol-induced neurodegeneration |
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| 500 | |a Date Revised 24.05.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 Walter de Gruyter GmbH, Berlin/Boston. | ||
| 520 | |a OBJECTIVES: The development of approaches to the treatment of neurodegenerative diseases caused by alcohol abuse by targeted pharmacological regulation of intracellular signaling transduction of progenitor cells of nerve tissue is promising. We studied peculiarities of participation of NF-кB-, сАМР/РКА-, JAKs/STAT3-, ERK1/2-, p38-pathways in the regulation of neural stem cells (NSC) and neuronal-committed progenitors (NCP) in the simulation of ethanol-induced neurodegeneration in vitro and in vivo | ||
| 520 | |a METHODS: In vitro, the role of signaling molecules (NF-кB, сАМР, РКА, JAKs, STAT3, ERK1/2, p38) in realizing the growth potential of neural stem cells (NSC) and neuronal-committed progenitors (NCP) in ethanol-induced neurodegeneration modeled in vitro and in vivo was studied. To do this, the method of the pharmacological blockade with the use of selective inhibitors of individual signaling molecules was used | ||
| 520 | |a RESULTS: Several of fundamental differences in the role of certain intracellular signaling molecules (SM) in proliferation and specialization of NSC and NCP have been revealed. It has been shown that the effect of ethanol on progenitors is accompanied by the formation of a qualitatively new pattern of signaling pathways. Data have been obtained on the possibility of stimulation of nerve tissue regeneration in ethanol-induced neurodegeneration by NF-кB and STAT3 inhibitors. It has been found that the blockage of these SM stimulates NSC and NCP in conditions of ethanol intoxication and does not have a «negative» effect on the realization of the growth potential of intact progenitors (which will appear de novo during therapy) | ||
| 520 | |a CONCLUSIONS: The results may serve as a basis for the development of fundamentally new drugs to the treatment of alcoholic encephalopathy and other diseases of the central nervous system associated with alcohol abuse | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a neural stem cells | |
| 650 | 4 | |a neurodegenerative diseases | |
| 650 | 4 | |a neuronal-committed progenitors | |
| 650 | 4 | |a neuroregeneration | |
| 650 | 4 | |a signaling transduction | |
| 650 | 4 | |a targeted therapy | |
| 650 | 7 | |a NF-kappa B |2 NLM | |
| 650 | 7 | |a Ethanol |2 NLM | |
| 650 | 7 | |a 3K9958V90M |2 NLM | |
| 700 | 1 | |a Miroshnichenko, Larisa Arkad Evna |e verfasserin |4 aut | |
| 700 | 1 | |a Simanina, Elena Vladislavovna |e verfasserin |4 aut | |
| 700 | 1 | |a Stavrova, Larisa Alexandrovna |e verfasserin |4 aut | |
| 700 | 1 | |a Polykova, Tatyana Yur Evna |e verfasserin |4 aut | |
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