Investigation of Possible Protective Effects of Certain Xenobiotics on Aluminum Toxicity in SH-SY5Y Cell Line

Abstract

Aluminum, a neurotoxic metal, is widely present in our daily lives, exposing us extensively. Aluminum exposure is a potential Alzheimer's risk factor, with no cure yet. Researchers are actively seeking new treatments or repurposing existing drugs to fight this challenging condition. This thesis explores metformin, naltrexone, and dihydrolipoic acid's neuroprotective potential on an Alzheimer's disease model (differentiated SH-SY5Y cells exposed to chronic aluminum). It delves into their impact on GSK-3β and Wnt signaling pathways. Results reveal that chronic aluminum exposure triggers oxidative stress, elevates tau protein levels, increases GSK-3β activity, and diminishes Wnt signaling pathway activity. Encouragingly, the studied xenobiotics promise to mitigate these detrimental effects. They effectively reduce tau protein levels, modulate GSK-3β and Akt activity, and restore Wnt signaling pathway functionality. Additionally, these compounds significantly alleviate oxidative stress, highlighting their potential as neuroprotective agents against chronic aluminum exposure in AD. In conclusion, further clinical investigations are essential to establish optimal dosages and treatment strategies. Dihydrolipoic acid may be a dietary supplement, potentially slowing AD progression when added to patient diets. Lower-dose naltrexone shows promise in mitigating neuroinflammation in Alzheimer's, warranting exploration as a novel therapy. Considering Alzheimer's as a metabolic disorder akin to diabetes, metformin emerges as a potential treatment. These findings highlight the need for urgent clinical trials and translational research, offering the potential to reshape AD treatment and provide renewed hope for patients and families.