College of Biotechnology and Pharmaceutical Engineering of West Anhui University, Lu'an 237012, PR China.
College of Biotechnology and Pharmaceutical Engineering of West Anhui University, Lu'an 237012, PR China; School of Pharmacy, Anhui University of Chinese medicine, Hefei 230031, PR China.
Brain Res. 2024 Nov 1;1842:149102. doi: 10.1016/j.brainres.2024.149102. Epub 2024 Jul 4.
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 Ca 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.
阿尔茨海默病（AD）是一种进行性神经退行性疾病。β-淀粉样蛋白（Aβ）在大脑中的积累已被认为是阿尔茨海默病（AD）发病和进展的关键因素。大脑中 Aβ 的积累会促进活性氧（ROS）的产生，进而引发 DNA、脂质和蛋白质等细胞成分的氧化损伤。在本研究中，我们研究了灵芝酸 A（GA.A）对 PC12 细胞中 Aβ42 诱导的细胞凋亡的保护作用。线粒体膜电位的变化表明，GA.A 通过减少 Aβ42 的沉积和抑制神经原纤维缠结的形成来治疗线粒体功能障碍。细胞内 Ca 和 caspase-3 的变化表明，GA.A 通过 Aβ42 减少了 PC12 细胞中的线粒体损伤，从而减少了 ROS 的积累并降低了 Aβ 原纤维诱导的细胞毒性。这些特征表明，GA.A 作为一种有效的神经保护药物，在治疗阿尔茨海默病方面具有巨大的潜力。
