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

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Abstract

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.

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Acknowledgments

This work was supported by a grant from the National Research Foundation of Korea (NRF) funded by the Korean Government (MRC 2011-0028213), by a grant (A101836) from the Korean Health Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea, and by the Priority Research Centres Program through the NRF funded by the Ministry of Education, Science and Technology (2012-0031403).

Conflict of Interest

The authors declare no conflicts of interest. All of the experimental procedures were approved by the Animal Care and Use Committee (IACUC) of Chungbuk National University (approval number CBNUA-144-1001-01).

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Authors and Affiliations

  1. College of Pharmacy and Medical Research Center, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763, South Korea

    Hyung-Mun Yun, Peng Jin, Jin-Yi Han, Sang-Bae Han, Ki-Wan Oh & Jin Tae Hong

  2. College of Agriculture, Life and Environment Sciences, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763, South Korea

    Moon-Soon Lee

  3. National Institute of Toxicological Research, Korea Food and Drug Administration, Seoul, South Korea

    Sung-Han Hong & Eun-Yong Jung

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  1. Hyung-Mun Yun
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Yun, HM., Jin, P., Han, JY. et al. Acceleration of the Development of Alzheimer’s Disease in Amyloid Beta-Infused Peroxiredoxin 6 Overexpression Transgenic Mice. Mol Neurobiol 48, 941–951 (2013). https://doi.org/10.1007/s12035-013-8479-6

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