Ganoderic acid a decreased Aβ42-induced neurotoxicity in PC12 cells by reduced mitochondrial damage

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. Accumulation of β-amyloid (Aβ) in the brain has been recognized as a key factor in the onset and progression of Alzheimer’s disease (AD).The accumulation of Aβ in the brain catalyzes the production of reactive oxygen species (ROS), which in turn triggers oxidative damage to cellular components such as DNA, lipids, and proteins. In the present study, we investigated the protective effect of Ganoderic acid A (GA.A) against Aβ42-induced apoptosis in PC12 cells. Changes in mitochondrial membrane potential indicated that GA.A treats mitochondrial dysfunction by decreasing Aβ42 deposition and inhibiting neural protofiber tangle formation. Changes in intracellular Ca2+ and caspase-3 indicated that GA.A reduced mitochondrial damage by Aβ42 in PC12 cells, thereby decreasing ROS accumulation and reducing Aβ protofiber-induced cytotoxicity. These features suggest that GA.A has great potential as an effective neuroprotective drug in the treatment of Alzheimer’s disease.