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

• Published in: Current molecular pharmacology Vol. 16; no. 2; p. 234
• Main Authors: Zyuz'kov, Gleb Nikolaevich, Miroshnichenko, Larisa Arkad'evna, Chayikovskyi, Alexander Vasil'evich, Kotlovskaya, Larisa Yur'evna
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.01.2023
• Subjects: Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Amyloid beta-Peptides - metabolism; Animals; Mice; Nerve Tissue - metabolism; NF-kappa B - metabolism; Signal Transduction; NF-κB; glial cells; neurodegenerative diseases; stem cells; Alzheimer's disease; signaling molecules
• ISSN: 1874-4702
• DOI: 10.2174/1874467215666220601144727

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. This study aims to test the hypothesis that NF-кB inhibitors are able to synchronize the activities of different types RCCs in AD. 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. 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. The results show the promise of developing a novel approach to Alzheimer's disease treatment with NF-κВ inhibitors.