Dihydrolipoic acid (DHLA) is a natural antioxidant known for its ability to counteract metal toxicity and oxidative stress. It has shown the potential to safeguard cells from harmful environmental substances. It may hold therapeutic benefits in treating neurodegenerative disorders by defending against oxidative damage and chronic inflammation. Thus, this study aimed to explore the potential neuroprotective effects of DHLA against aluminum (Al)-induced toxicity using an Alzheimer's disease (AD) model in vitro. The study focused on two important pathways: GSK-3β and the Wnt signaling pathways. The SH-SY5Y cell line was differentiated to establish AD, and the study group were as follows: control, Al, DHLA, Al-DHLA, AD, AD-Al, AD-DHLA, and AD-Al-DHLA. The impact of DHLA on parameters related to oxidative stress was assessed. The activity of the GSK-3β pathway was measured by evaluating the levels of PPP1CA, PP2A, GSK-3β, and Akt. The Wnt signaling pathway was assessed by measuring Wnt/β-catenin in the different study groups. Exposure to DHLA significantly reduced oxidative stress by effectively decreasing the levels of reactive oxygen species, thereby protecting against protein oxidation and limiting the production of malonaldehyde. Moreover, the DHLA-treated groups exhibited a remarkable increase in the total antioxidant capacity. Furthermore, the study observed an upregulation of the Wnt signaling pathway and a downregulation of the GSK-3β pathway in the groups treated with DHLA. In summary, the neuroprotective effects of DHLA, primarily achieved by reducing oxidative stress and modulating critical imbalanced pathways associated with AD, indicate its potential as a promising addition to the treatment regimens of AD patients.
Keywords: Alzheimer; GSK-3β; Wnt signaling; aluminum; dihydrolipoic acid; neuroprotection.
© 2023 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd.