S-allyl cysteine and alliin enhance catalase activity and prevent aggregation to counter oxidative stress in alzheimer's disease.

Oxidative stress is a key driver of Alzheimer's disease (AD), often linked to reduced activity of catalase, a major antioxidant enzyme. In AD, catalase is not only less active but also found as part of harmful protein aggregates with amyloid-β in brain plaques. Finding safe molecules that can boost catalase activity and stop it from aggregating could, therefore, offer a new strategy to lower disease progression. In this study, we examined two natural organosulfur compounds from garlic-S-allyl cysteine (SAC) and Alliin-for their effects on catalase. We found that both compounds significantly increased catalase activity in a concentration-dependent manner by stabilizing its structure and enhancing its thermodynamic stability. Furthermore, Molecular docking and Simulation studies revealed that SAC and Alliin bind at an allosteric site, promoting structural compaction and enhancing stability. Importantly, these compounds also reduced the tendency of catalase to form amyloid-like aggregates, a feature directly relevant to AD pathology. Our findings provide new mechanistic insights into how SAC and Alliin act on catalase-both stabilizing the enzyme and resulting in an increase in its activity along with lowering its aggregation propensity. This suggests that SAC and Alliin may serve as promising, natural candidates for therapeutic intervention in Alzheimer's disease.