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Title 

Peroxiredoxin 5 decreases beta-amyloid-mediated cyclin-dependent kinase 5 activation through regulation of Ca2+-mediated calpain activation

Authors 

J H ParkB KimU ChaeD G LeeM K KamSang-Rae LeeS LeeH S LeeJ W ParkD S Lee

Publisher 

Mary Ann Liebert

Issue Date 

2017

Citation 

Antioxidants and Redox Signaling

Keywords 

Alzheimer's diseasecalciumcalpainCdk5oxidative stressperoxiredoxin

Abstract 

Aims: 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

ISSN 

1523-0864

Link 

http://dx.doi.org/10.1089/ars.2016.6810

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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