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Abstract

Background

p53 is a transcriptional factor that regulates numerous cellular processes, the stability and activity of p53 is essential to maintain its function. Post-translational modifications (PTMs), particularly SUMOylation, play a vital role in regulating p53 activity.

Objective

To investigate the neurogenesis related genes that downregulated by p53 SUMOylation in APP/PS1 mice, and the protected effect by overexpressing non-SUMOylated p53 (p53 K386R). Furthermore, to provide new clues for the mechanisms of Alzheimer's disease (AD).

Methods

Co-immunoprecipitation was used to detect the p53 SUMOylation levels in neuro2a (N2a) cells and APP/PS1 mice overexpressing wild-type p53 (p53 WT) or p53 K386R. In addition, RNA sequencing (RNA-seq) was used to detect the p53 SUMOylation regulated genes. Then we used qPCR, western blot, and immunofluorescence to measure the expression of neuroglobin (ngb) and the effect of neurogenesis defects induced by p53 SUMOylation.

Results

We verified that overexpression of p53 WT promoted p53 SUMOylation and p53 K386R decreased p53 SUMOylation in N2a cells and APP/PS1 mice. Ngb was related to neurogenesis which dramatically downregulated by p53 SUMOylation. In addition, we found p53 SUMOylation caused neuron reduction and impairment of neurogenesis.

Conclusions

Our data support that p53 SUMOylation may lead to neurogenesis defects by downregulating ngb in AD, suggesting that inhibition of p53 SUMOylation may be served as a therapeutic strategy for preventing AD and provide a new target for future researches and interventions.

Keywords

Alzheimer's disease neurogenesis neuroglobin (ngb)p53 SUMOylation

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p53 SUMOylation promotes neurogenesis defects in APP/PS1 mice

Abstract

Background

Objective

Methods

Results

Conclusions

Keywords

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References