Acceleration of the Development of Alzheimer's Disease in Amyloid Beta-Infused Peroxiredoxin 6 Overexpression Transgenic Mice

The amyloid beta (A beta) peptide in the brains of patients with Alzheimer's disease (AD) is cytotoxic to neurons and has a central role in the pathogenesis of the disease. Peroxiredoxin 6 (Prdx6) is an antioxidant protein and could act as a cytoprotective protein. However, the role of Prdx6 in neurodegenerative disease has not been studied. Thus, the roles and action mechanisms in the development of AD were examined. A beta(1-42)-induced memory impairment in Prdx6 transgenic mice was worse than C57BL/6 mice, and the expression of amyloid precursor protein cleavage, C99, beta-site APP-cleaving enzyme 1, inducible nitric oxide synthase, and cyclooxygenase-2 was greatly increased. In addition, the astrocytes and microglia cells of A beta-infused Prdx6 transgenic mice were more activated, and A beta also significantly increased lipid peroxidation and protein carbonyl levels, but decreased glutathione levels. Furthermore, we found that translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus was increased in A beta-infused Prdx6 transgenic mice. These results suggest that the overexpression of Prdx6 could accelerate the development of AD through increased amyloidogenesis through independent PLA2 activation and Nrf2 transcription.