Prospects for the Therapeutic Potential of Inhibitors Targeting JNK and p53 in Alzheimer's Disease
Abstract
Background: It is promising to search for fundamentally new approaches to the treatment of Alzheimer's disease (AD) within the framework of creating methods for stimulating neurogenesis and developing a strategy for targeted pharmacological regulation of intracellular signal transduction in regenerative-competent cells (RCCs). Of particular interest in this case are JNK and p53. The purpose of the work was to investigate the possibility of regulating the RCCs functions using JNK and p53 inhibitors in the modelling β-amyloid-induced neurodegeneration (βAIN) in vitro.
Methods: The studies were performed using C57BL/6 mice. To model βAIN in vitro, the 25-35 fragment Amyloid β(βA) was used. The effect of the JNK inhibitors (SP600125) and p53 (Pifithrin-a, Cyclic) on the functioning of different types of progenitors and glial cells of the subventricular zone of the cerebral hemispheres (SVZ)was studied. NPCs, astrocytes, oligodendrocytes, and microglial cells were isolated from SVZ cells using immunomagnetic separation.
Results: We found the ability of the JNK inhibitor to stimulate the proliferation of NSCs and NPCs in βAIN simulation. While the p53 inhibitor is characterized by stimulatory activity in relation to the proliferation of only committed neuronal precursors under conditions of neurotoxic exposure to βA. In addition, inhibition of JNK and p53 resulted in stimulation of the secretion of neurotrophins by oligodendrocytes and microglial cells in the in vitro βAIN model.
Conclusion: The results indicate the potential ability of the JNK inhibitor to most consistently stimulate the implementation of the proregenerative properties of progenitor and neuroglial cells in AD.
Keywords: Alzheimer's disease; Neural stem cells; β-amyloid; JNK, p53
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DOI: http://dx.doi.org/10.62940/als.v10i2.1803
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