title: Acceleration of the development of Alzheimer's disease in amyloid beta-infused peroxiredoxin 6 overexpression transgenic mice.
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.
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763, South Korea.
authors.forename: Hyung-Mun
authors.initials: HM
authors.lastname: Yun
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.forename: Jin-Yi
authors.initials: JY
authors.lastname: Han
authors.forename: Moon-Soon
authors.initials: MS
authors.lastname: Lee
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Han
authors.forename: Ki-Wan
authors.initials: KW
authors.lastname: Oh
authors.forename: Sung-Han
authors.initials: SH
authors.lastname: Hong
authors.forename: Eun-Yong
authors.initials: EY
authors.lastname: Jung
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000201:enzymology / Q000473:pathology*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008569:Memory Disorders / Q000150:complications / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D054465:Peroxiredoxin VI / Q000378:metabolism*; D054467:Phospholipases A2 / Q000378:metabolism; D050050:Protein Carbonylation / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D054465:Peroxiredoxin VI; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D054467:Phospholipases A2; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse; D005978:Glutathione