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

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 ß-amyloid-induced neurodegeneration (ßAIN) in vitro. RESULTS: We showed that ß-amyloid (Aß) causes divergent changes in the functioning of NSCs and NCPs. Also demonstrated that different populations of neuroglia respond differently to exposure to Aß. 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 ßAIN. CONCLUSION: The results show the promise of developing a novel approach to Alzheimer's disease treatment with NF-κВ inhibitors.