Antioxidant dihydrolipolic acid protects against aluminum-induced toxicity in Alzheimer's model

Abstract Dihydrolipoic acid (DHLA) is a natural antioxidant that is recognized as being useful in combating metal toxicity and oxidative stress. It can protect cells from environmental contaminants and may be beneficial in treating neurodegenerative diseases by protecting against oxidative damage and chronic inflammation. Therefore, this study aimed to investigate the possible neuroprotective effects of DHLA against aluminum-induced toxicity in an in vitro Alzheimer’s disease (AD) model. The study focused on the glycogen synthase kinase3 (GSK3) pathway, and the Wnt signaling. A differentiated SH-SY5Y cell line model of AD was developed, and the study groups were as follows: control, Al, DHLA, Al-DHLA, AD, AD-Al, AD-DHLA, and AD-Al-DHLA. The impact of DHLA on oxidative stress parameters was evaluated, and GSK3 pathway was evaluated by measuring GSK3-β, human serine/threonine-protein phosphatase PP1-alpha catalytic subunit (PPP1CA), protein phosphatase 2A (PP2A) levels, and human RAC-alpha serine/threonine-protein kinase (AKT1). The Wnt signaling pathway was evaluated by measuring canonical Wingless and Int-1/β-catenin (Wnt/β-catenin) on different study groups. Exposure to DHLA reduced oxidative stress by dramatically lowering reactive oxygen species levels, protecting against protein oxidation, and limiting malonaldehyde production. Additionally, the total antioxidant capacity of DHLA-treated groups increased drastically. Furthermore, upregulation of Wnt signaling and downregulation of GSK3 pathways were observed in the groups treated by DHLA. Overall, the neuroprotective effects of DHLA, especially by reducing oxidative stress and regulating key imbalanced pathways in AD disease, make it a good candidate to be added to AD patients' treatment regimens.