Acceleration of the development of Alzheimer's disease in amyloid beta-infused peroxiredoxin 6 overexpression transgenic mice.

The amyloid beta (Aβ) 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. Aβ1-42-induced memory impairment in Prdx6 transgenic mice was worse than C57BL/6 mice, and the expression of amyloid precursor protein cleavage, C99, β-site APP-cleaving enzyme 1, inducible nitric oxide synthase, and cyclooxygenase-2 was greatly increased. In addition, the astrocytes and microglia cells of Aβ-infused Prdx6 transgenic mice were more activated, and Aβ 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 Aβ-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.