Generation of reactive oxygen species and activation of NF-κB by non-Aβ component of Alzheimer's disease amyloid

摘要: Non-amyloid beta (Abeta) component of Alzheimer's disease (AD) amyloid (NAC) coexists with Abeta protein in senile plaques. After exposure to NAC fibrils, cortical neurons rat brain primary culture became apoptotic, while astrocytes were activated extension their processes. fibrils decreased the activity reducing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) more markedly (IC(50) = 5.6 microm) than approximately 50 microm). The neuron-specific toxicity was indicated also by an increased release lactate dehydrogenase from cells. Neuronal apoptosis suppressed pre-treatment antioxidants, propyl gallate (PG) and N-t-butyl-phenylnitrone (BPN), or overexpression human Bcl-2. Exposure enhanced generation reactive oxygen species (ROS) less efficiently astrocytes, as demonstrated oxidation 2',7'-dichlorofluorescin. site ROS shown be mitochondria chloromethyl-tetramethyl rosamine. nuclear translocation factor kappa B (NF-kappaB) its DNA-binding activity, which inhibited PG BPN astrocytes. These results suggest that increase mitochondrial activate NF-kappaB, thereby causing a differential change gene expression between AD brain.