Anti-amyloidogenic activity of S-allyl-L-cysteine and its activity to destabilize Alzheimer's beta-amyloid fibrils in vitro.
Alzheimer's disease involves Abeta 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 Abeta 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 Abeta induced neuronal apoptosis. Hence, we investigated the effects of SAC on Abeta aggregation by employing Thioflavin-T, transmission electron microscopy, SDS-PAGE, size exclusion-HPLC. Under aggregating conditions in vitro, SAC dose-dependently inhibited Abeta fibrillation and also destabilized preformed Abeta fibrils. Further, Circular dichroism and fluorescence quenching studies supported the binding ability of SAC to Abeta and inducing a partially folded conformation in Abeta. The 3D structure of Abeta-SAC complex was also predicted employing automated docking studies.
Gupta
Veer Bala
VB
Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore 570020, India.
Rao
K S J
KS
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology; D052160:Benzothiazoles; D003545:Cysteine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D046911:Macromolecular Substances / Q000737:chemistry / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D018696:Neuroprotective Agents / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation / Q000187:drug effects; D017510:Protein Folding; D013844:Thiazoles / Q000737:chemistry
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D052160:Benzothiazoles; D046911:Macromolecular Substances; D018696:Neuroprotective Agents; D013844:Thiazoles; C009462:thioflavin T; C065299:S-allylcysteine; D003545:Cysteine