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Effects of δ-Catenin on APP by Its Interaction with Presenilin-1

  • Dai, Weiye (College of Pharmacy and Research Institute for Drug Development, Chonnam National University) ;
  • Ryu, Taeyong (College of Pharmacy and Research Institute for Drug Development, Chonnam National University) ;
  • Kim, Hangun (College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University) ;
  • Jin, Yun Hye (College of Pharmacy and Research Institute for Drug Development, Chonnam National University) ;
  • Cho, Young-Chang (College of Pharmacy and Research Institute for Drug Development, Chonnam National University) ;
  • Kim, Kwonseop (College of Pharmacy and Research Institute for Drug Development, Chonnam National University)
  • Received : 2018.06.25
  • Accepted : 2018.10.18
  • Published : 2019.01.31

Abstract

Alzheimer's disease (AD) is the most frequent age-related human neurological disorder. The characteristics of AD include senile plaques, neurofibrillary tangles, and loss of synapses and neurons in the brain. ${\beta}-Amyloid$ ($A{\beta}$) peptide is the predominant proteinaceous component of senile plaques. The amyloid hypothesis states that $A{\beta}$ initiates the cascade of events that result in AD. Amyloid precursor protein (APP) processing plays an important role in $A{\beta}$ production, which initiates synaptic and neuronal damage. ${\delta}-Catenin$ is known to be bound to presenilin-1 (PS-1), which is the main component of the ${\gamma}-secretase$ complex that regulates APP cleavage. Because PS-1 interacts with both APP and ${\delta}-catenin$, it is worth studying their interactive mechanism and/or effects on each other. Our immunoprecipitation data showed that there was no physical association between ${\delta}-catenin$ and APP. However, we observed that ${\delta}-catenin$ could reduce the binding between PS-1 and APP, thus decreasing the PS-1 mediated APP processing activity. Furthermore, ${\delta}-catenin$ reduced PS-1-mediated stabilization of APP. The results suggest that ${\delta}-catenin$ can influence the APP processing and its level by interacting with PS-1, which may eventually play a protective role in the degeneration of an Alzheimer's disease patient.

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Fig. 1. The interaction between APP, δ-catenin, and PS-1.

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Fig. 2. The binding between APP and PS1 is reduced by δ-catenin in a dose-dependent manner.

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Fig. 3. δ-Catenin-mediated alteration of APP protein levels and processing.

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Fig. 4. δ-Catenin overexpression-mediated alteration of C99 expression.

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Fig. 5. δ-Catenin-related reduction of PS1-mediated stabilization on APP (C99).

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Fig. 6. δ-Catenin-mediated decrease of APP (C99) protein stability.

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Fig. 7. A proposed model illustrates how δ-catenin regulates APP processing.

Acknowledgement

Supported by : National Research Foundation of Korea (NRF)

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