Altered gene expression associated with Alzheimer's disease in the SH-SY5Y neuroblastoma cell model: Enhanced intracellular GSK3β and Cyclophilin A, as key neuropathology-inducing factors.

Glycogen synthase kinase 3β (GSK3β) has been shown to play a role in the pathophysiology of Alzheimer's disease (AD). Another important factor in the pathophysiology of AD is Cyclophilin A (CypA). The objective of this study is to evaluate the impact of enhanced intracellular levels of these two macromolecules on the expression of genes associated with AD and Tau protein phosphorylation in SH-SY5Y cells. According to RT-qPCR results, GSK3β and CypA significantly affect the mRNA expression of genes involved in AD development, including those associated with multiple signaling pathways, such as inflammation, cell death, and Tau protein phosphorylation (P < 0.05). Western blot analyses also revealed changes in Tau protein behavior, explained by alterations in phosphorylation at specific sites modified under the effect of GSK3β and CypA (P < 0.05). Network analysis identified amyloid beta precursor protein (APP) as the most prominent of the 17 frequently impacted genes by GSK3β and CypA. Mitogen-Activated Protein Kinases (MAPKs), cytosol, kinase binding, and regulation of apoptotic processes represent the key signaling pathways, cellular components, molecular functions, and biological processes involved. The results of the current study demonstrate that GSK3β and CypA contribute to clarifying the mechanisms underlying AD pathophysiology in cellular studies related to this disorder.