PKA Inhibition in Alzheimer's Disease: Through the Apologia of a Straight Forward but Nontrivial Concept of Targeting Intracellular Signal Transduction to the Prologue to the Era of Novel Drugs

A promising approach for the treatment of neurodegenerative diseases, including the treatment of Alzheimer's disease (AD), maybe “Targeted regulation of intracellular signal transduction in the regeneration-competent cells (RCCs).” The aim of the work was to study the pharmacological (including neuroregenerative) effects of the PKA inhibitor (KT 5720) in a mouse model of AD. Based on research results and analysis of previously obtained data, it was proposed for the first time to consider the intracellular signal transduction system as a deterministic chaotic system. The reasons for the development of the “butterfly effect” and “fluctuations” in its activity, as well as factors for compensation of the latter and stability of functioning (self-organization and emergence), are presented. At the same time, pronounced therapeutic effects of the PKA inhibitor were shown in aged C57BL/6 mice (characterized by a high level of pathological endogenous β-amyloid formation in the brain). The correction of disorders of their cognitive and emotional status was discovered. It was revealed that the development of these effects is based on the coordination of the activities of different types of nervous tissue progenitors, coupled with the leveling of the pathological reaction of astroglia and microglia. The morphological signs of the antisenescence effect of the pharmacological agent on some other organs and a significant increase in the life expectancy of experimental animals treated with the PKA inhibitor were also found. The findings indicate the possibility of creating on its basis not only a medicine for AD treatment but also anti-aging drugs. Controlling the regenerative potential of tissues through targeted regulation of intracellular signal transduction in the RCCs represents a promising new paradigm for a pharmacological strategy for regenerative medicine.