1. Joseph Lucas
Qitao Ran, Ph.D
Department of Cellular and Structural Biology
Investigation of the molecular mechanisms underlying the neuroprotective
effect of Peroxiredoxin 3 against paraquat-induced cognitive impairment
Co-authors: Luiji Chen, Ren Na, Yan Lai
Alzheimer’s disease (AD) affects more than 5 million Americans and is currently the 6th leading
cause of death in the world. Although the etiology of AD remains unclear, exposure to
pesticides such as paraquat has been shown to increase the risk of AD through epidemiological
studies. In a previous study, increased levels of H2O2 in the mitochondria from paraquat
exposure exasperated mitochondrial oxidative damage and cognition decline. It was also shown
that Peroxiredoxin 3 (Prdx3), a mitochondrial antioxidant defense enzyme vital for H2O2
removal, protected against paraquat-induced cognitive impairment. This project focused on
investigating the specific molecular mechanisms underlying Prdx3 protection. We hypothesized
that overexpression of Prdx3 protected against paraquat-induced cognition decline through
mechanisms such as attenuated oxidative damage, reduced inflammation, altered apoptosis
and/or autophagy. By western blot, we first looked at Prdx3 expression in wildtype mice (WT),
wildtype mice exposed to paraquat (WT-PQ), PRDX3 transgenic mice (PRDX3), and Prdx3
transgenic mice exposed to paraquat (PRDX3-PQ). Prdx3 protein was shown to be elevated in
PRDX3 mice as expected (see figure below). We next measured for 4-HNE, a marker of oxidative
damage, but no large differences in 4-HNE were observed among the groups. We also
compared levels of inflammation by measuring caspase-1 and IL-1β levels. Again, no significant
differences in levels of activated caspase-1 or IL-1β were observed among the groups. Future
investigation will use real time PCR, to analyze levels of apoptosis and autophagy in these four
groups of mice. We hope that this data will give insight into the protective effect of Prdx3
overexpression
