PTEN inhibition induces neuronal differentiation and neuritogenesis in SH-SY5Y cells via AKT signaling pathway

Abstract

BackgroundPTEN is a key regulator of neuronal differentiation and neurogenesis. Its role in modulating the PI3K/AKT pathway and oxidative stress responses in neuronal models remains an area of active investigation.ObjectiveThis study aimed to assess the effects of PTEN knockdown on neuronal differentiation, neuritic growth, and PI3K/AKT pathway activation in SH-SY5Y cells.MethodsSH-SY5Y cells were treated with PTEN siRNA to induce PTEN knockdown. The level of PTEN inhibition was confirmed, and assays were performed to evaluate neurogenesis and neuritogenesis at 3- and 7-days post-treatment. Protein expression analysis of key components in the AKT/GSK3-β/Tau pathway was conducted to assess their role in neurogenesis. Additionally, the PI3K inhibitor LY294002 was used to examine its impact on PTEN knockdown-induced neuronal differentiation.ResultsPTEN knockdown significantly increased neurite lengths and reduced cytoplasmic size, indicating neuronal differentiation. Protein analysis showed that PTEN inhibition modulated the expression of components in the AKT/GSK3-β/Tau pathway. The PI3K inhibitor LY294002 prevented neuronal differentiation, confirming the involvement of the PI3K/AKT pathway in mediating the effects of PTEN knockdown.ConclusionsOur findings demonstrate that PTEN plays a crucial role in regulating neuronal differentiation in SH-SY5Y cells. The PI3K/AKT pathway mediates the effects of PTEN knockdown, suggesting PTEN as a potential therapeutic target for neurodegenerative diseases where its dysregulation may contribute to disease progression.

Keywords: Alzheimer's disease; PI3K/AKT pathway; PTEN knockdown; tau phosphorylation.