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Current Molecular Pharmacology

Author(s): Gleb Nikolaevich Zyuz’kov*, Larisa Arkad’evna Miroshnichenko, Alexander Vasil’evich Chayikovskyi and Larisa Yur’evna Kotlovskaya

DOI: 10.2174/1874467215666220601144727

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Nf-κb: A Target for Synchronizing the Functioning Nervous Tissue Progenitors of Different Types in Alzheimer's Disease

Article ID: e010622205529 Pages: 8

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Abstract

Background: The efficacy of Alzheimer's disease (AD) treatment can be enhanced by developing neurogenesis regulation approaches by synchronizing regenerative-competent cell (RCCs) activity. As part of the implementation of this direction, the search for drug targets among intracellular signaling molecules is promising.

Objective: This study aims to test the hypothesis that NF-кB inhibitors are able to synchronize the activities of different types RCCs in AD.

Methods: The effects of NF-κB inhibitor JSH-23 on the functioning of neural stem cells (NSCs), neuronal-committed progenitors (NCPs), and neuroglial cells were studied. Individual populations of C57B1/6 mice brain cells were obtained by immunomagnetic separation. Studies were carried out under conditions of modeling β-amyloid-induced neurodegeneration (βAIN) in vitro.

Results: We showed that β-amyloid (Aβ) causes divergent changes in the functioning of NSCs and NCPs. Also demonstrated that different populations of neuroglia respond differently to exposure to Aβ. These phenomena indicate a significant discoordination of the activities of various RCCs. We revealed an important role of NF-κB in the regulation of progenitor proliferation and differentiation and glial cell secretory function. It was found that the NF-κB inhibitor causes synchronization of the pro-regenerative activities of NSCs, NCPs, as well as oligodendrocytes and microglial cells in βAIN.

Conclusion: The results show the promise of developing a novel approach to Alzheimer's disease treatment with NF-κВ inhibitors.

Keywords: Alzheimer's disease, stem cells, glial cells, neurodegenerative diseases, NF-κB, signaling molecules.

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