title: Peroxiredoxin 5 Decreases Beta-Amyloid-Mediated Cyclin-Dependent Kinase 5 Activation Through Regulation of Ca2+-Mediated Calpain Activation.
abstract: OBJECTIVE
  Aberrant Cdk5 (cyclin-dependent kinase 5) and oxidative stress are crucial components of diverse neurodegenerative disorders, including Alzheimer's disease (AD). We previously reported that a change in peroxiredoxin (Prx) expression is associated with protection from neuronal death. The aim of the current study was to analyze the role of Prx in regulating Cdk5 activation in AD.
  
  
  RESULTS
  We found that of the six Prx subtypes, Prx5 was increased the most in cellular (N2a-APPswe cells) model of AD. Prx5 in the brain of APP (amyloid precursor protein) transgenic mouse (Tg2576) was more increased than a nontransgenic mouse. We evaluated Prx5 function by using overexpression (Prx5-WT), a mutation in the catalytic residue (Prx5-C48S), and knockdown. Increased neuronal death and Cdk5 activation by amyloid beta oligomer (AβO) were rescued by Prx5-WT expression, but not by Prx5-C48S or Prx5 knockdown. Prx5 plays a role in Cdk5 regulation by inhibiting the conversion of p35 to p25, which is increased by AβO accumulation. Prx5 is also upregulated in both the cytosol and mitochondria and it protects cells from AβO-mediated oxidative stress by eliminating intracellular and mitochondrial reactive oxygen species. Moreover, Prx5 regulates Ca2+and Ca2+-mediated calpain activation, which are key regulators of p35 cleavage to p25. Innovation and Conclusion: Our study represents the first demonstration that Prx5 induction is a key factor in the suppression of Cdk5-related neuronal death in AD and we show that it functions via regulation of Ca2+-mediated calpain activation. Antioxid. Redox Signal. 27, 715-726.
authors.affiliation: 1 School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University , Daegu, Republic of Korea.|2 College of Natural Sciences, Kyungpook National University , Daegu, Republic of Korea.
authors.forename: Junghyung
authors.initials: J
authors.lastname: Park
authors.affiliation: 1 School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University , Daegu, Republic of Korea.|2 College of Natural Sciences, Kyungpook National University , Daegu, Republic of Korea.
authors.forename: Bokyung
authors.initials: B
authors.lastname: Kim
authors.affiliation: 1 School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University , Daegu, Republic of Korea.|2 College of Natural Sciences, Kyungpook National University , Daegu, Republic of Korea.
authors.forename: Unbin
authors.initials: U
authors.lastname: Chae
authors.affiliation: 1 School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University , Daegu, Republic of Korea.|2 College of Natural Sciences, Kyungpook National University , Daegu, Republic of Korea.
authors.forename: Dong Gil
authors.initials: DG
authors.lastname: Lee
authors.affiliation: 1 School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University , Daegu, Republic of Korea.|2 College of Natural Sciences, Kyungpook National University , Daegu, Republic of Korea.
authors.forename: Min Kyoung
authors.initials: MK
authors.lastname: Kam
authors.affiliation: 3 National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB) , Cheongju, Republic of Korea.
authors.forename: Sang-Rae
authors.initials: SR
authors.lastname: Lee
authors.affiliation: 4 Animal Biotechnology Division, National Institute of Animal Science , Jeonju, Republic of Korea.
authors.forename: Seunghoon
authors.initials: S
authors.lastname: Lee
authors.affiliation: 1 School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University , Daegu, Republic of Korea.|2 College of Natural Sciences, Kyungpook National University , Daegu, Republic of Korea.
authors.forename: Hyun-Shik
authors.initials: HS
authors.lastname: Lee
authors.affiliation: 1 School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University , Daegu, Republic of Korea.|2 College of Natural Sciences, Kyungpook National University , Daegu, Republic of Korea.
authors.forename: Jeen-Woo
authors.initials: JW
authors.lastname: Park
authors.affiliation: 1 School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University , Daegu, Republic of Korea.|2 College of Natural Sciences, Kyungpook National University , Daegu, Republic of Korea.
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Lee
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D002460:Cell Line; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D054464:Peroxiredoxins / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D016229:Amyloid beta-Peptides; C515974:PRDX5 protein, human; D054464:Peroxiredoxins; D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human; D002154:Calpain; D002118:Calcium
keywords: Alzheimer's disease; Cdk5; calcium; calpain; oxidative stress; peroxiredoxin