The Role of cAMP-Dependent Intracellular Signaling Pathways in the Regulation of the Functions of Neural Stem Cells and Neuroglial Cells in Amyloid-[beta]-Induced Neurodegeneration

Under conditions of neurodegeneration modeled in vitro by the [beta]-amyloid peptide-(25-35) fragment (A[[beta].sub.325-35]), we studied the role of individual links of cAMP-dependent intracellular signaling pathways in determining the proliferation and differentiation status of neural stem cells (NSCs) and colony-stimulating activity of supernatants from neuroglial cells. The important role of intracellular cAMP and PKA in the inhibition of the progression of the NSC cell cycle and stimulation of the process of their specialization induced by A[[beta].sub.325-35] was found. The selective ability of PKA to block the production of factors constituting colony-stimulating activity by neuroglial cells under conditions of their cultivation in vitro with a neurotoxic agent was revealed. Our results suggests that inhibitors of adenylate cyclase and PKA can increase the degree of implementation of the growth potential of NSCs and conjugation of the processes of their proliferation and differentiation in Alzheimer's disease. At the same time, selective PKA blockers can also induce the production of NSC-stimulating factors by neuroglial cells. Key Words: Alzheimer's disease; neural stem cells; [beta]-amyloid; cAMP; PKA