Anti-amyloidogenic activity of S-allyl-l-cysteine and its activity to destabilize Alzheimer's β-amyloid fibrils in vitro

Alzheimer's disease involves Aβ accumulation, oxidative damage and inflammation and there is currently no clinically accepted treatment to stop its progression. Its risk is known to reduce with increased consumption of antioxidant and anti-inflammatory agents. Fibrillar aggregates of Aβ are major constituents of the senile plaques found in the brains of AD patients and have been related to AD neurotoxicity. It is reported that SAC (S-allyl-l-cysteine), a water-soluble organosulfur component present in garlic is known to prevent cognitive decline by protecting neurons from Aβ induced neuronal apoptosis. Hence, we investigated the effects of SAC on Aβ aggregation by employing Thioflavin-T, transmission electron microscopy, SDS-PAGE, size exclusion-HPLC. Under aggregating conditions in vitro, SAC dose-dependently inhibited Aβ fibrillation and also destabilized preformed Aβ fibrils. Further, Circular dichroism and fluorescence quenching studies supported the binding ability of SAC to Aβ and inducing a partially folded conformation in Aβ. The 3D structure of Aβ-SAC complex was also predicted employing automated docking studies. © 2007 Elsevier Ireland Ltd. All rights reserved.