Low Dose Pioglitazone Attenuates Oxidative Damage in Early Alzheimer's Disease by Binding mitoNEET: Transcriptome-To-Reactome~(™) Biosimulation of Neurons

摘要

Oxidative damage (OD) is considered to be a central component in the progression of Alzheimer 's disease (AD). 8-hydroxyguanosine (8-OHG), a readily oxidized ribonucleic acid found in AD, was used as a biomarker to investigate the role of OD in the progression of the disease. A disruption in two critical Thioredoxin-Dependent Peroxiredoxin System components, peroxiredoxin-3 (Prx-3) and thioredoxin (Trx), may serve as a source of the increased accumulation of OD observed in AD. We demonstrate that OD, in the form of 8-OHG, was quantitatively most significant during the earliest stage of AD [F (3, 25) =5.08,p<. 01]. A drastic decline in mitochondrial protein levels of Prx-3 [F (3, 25) = 8.74, p. < 01] and Trx [F (3, 25) = 4.33, p. < 05] were also observed across the progression of the disease. We then tested the efficacy of pioglitazone, a thiazolidinedione class drug aimed to delay onset of AD by acting on mitoNEET. Our results showed a significant reduction in the oxidized variant of mitoNEET within the incipient population when a 0.8mg dose was simulated in silico (p = 0.0242; a. < 05).