The Antioxidant Mechanisms Underlying the Aged Garlic Extract- and S-Allylcysteine-Induced Protection
S-allylcysteine (SAC) prevents the progression of Alzheimer’s disease (AD) by multiple mechanisms: (1) antioxidant, SAC scavenges free radicals and oxidant specie (direct antioxidant) and restores glutathione peroxidase, glutathione reductase, and superoxide dismutase levels (indirect antioxidant). Consequently, SAC diminishes lipid peroxidation, DNA fragmentation, protein oxidation, and endoplasmic reticulum (ER) stress. The decrease in endoplasmic reticulum stress attenuates Ca2+ release and the subsequent activation of calpain and the caspase-12-dependent pathway, which altogether decrease the cell death; (2) antiamyloidogenic, SAC decreases Aβ formation and/or increases Aβ clearance. SAC lowers amyloid precursor protein (APP) mRNA expression, BACE (β-site APP cleavage enzyme 1) expression and activity and restores PKC activity under AD-like condition, which benefits APP cleavage and decreases the available APP for Aβ. In addition, SAC can bind to Aβ-inhibiting Aβ fibrillation and destabilizing preformed Aβ-peptide fibrils; (3) anti-inflammatory, SAC decreases IL-1β and TNF-α levels and IL-1β-positive plaque-associated microglia; (4) antitangle, SAC reduces tau2 reactivity and its phosphorylation; this reduction in tau appears to involve GSK-3β protein; (5) anti-glycative; SAC declines both activity and mRNA expression of aldose reductase (AR), which subsequently decreases the production of sorbitol and prevents advanced glycation end products (AGEs) formation, such as carboxymethyllysine (CML) and pentosidine, decreasing glycative stress.
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