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

Abstract

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.