Wnt / ß-Catenin Signaling Pathway Against Aβ Toxicity in PC12 Cells.

Abstract

Background/aims: Alzheimer's disease (AD) is characterized by accumulation of β-amyloid (Aβ), However, the mechanism of how Aβ affects neuronal cell death remains elusive. The balance of pro- and anti-apoptotic Bcl-2 family proteins (e.g., Bcl-2 and Bax) has been known to play a pivotal role in neuronal cell death. Of note, expression levels of these proteins are changed in the neurons in AD. To date no study has elusidated the relationship between Aβ and Bax.

Methods: The present study explored the role of Wnt/β-catenin pathway in the neurotoxic effect of Aβ25-35. Flow cytometry was employed to determine the apoptosis, western blotting to assess the protein abundance of Bcl-2 and BAX, MTT assay to decipher the cells viability.

Results: As a result, the addition of Wnt3a significantly prevented oligomeric Aβ-induced neuronal cell death and viability. Furthermore, treatment with Aβ25-35 increased Bax and Bcl-2 protein abundance and mRNA levels, an effect significantly blocked by Wnt3a (100 ng/ml) and GSK3β inhibitor TWS119 (10µM).

Conclusion: These findings are first to demonstrate that Wnt/β-catenin signaling pathway regulates Aβ25-35-induced apoptosis.