Affiliation:
1. Tomsk National Research Medical Center, Goldberg Research Institute of Pharmacology and Regenerative Medicine,
Tomsk Russian Federation
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-кB 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-кB in the regulation of progenitor proliferation and
differentiation and glial cell secretory function. It was found that the NF-кB 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-кВ inhibitors.
Funder
Russian Science Foundation
Publisher
Bentham Science Publishers Ltd.
Subject
General Health Professions
Cited by
10 articles.
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