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GLP-1 Receptor Agonist Inhibited the Activation of RIPK1 for Alleviation the Neuronal Death and Neuroinflammation in APP/PS1 Mice

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A Correction to this article was published on 26 May 2022

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Abstract

Alzheimer’s disease (AD) is characterized by neuronal necroptosis and neuroinflammation, retardation of these pathological development was considered to play crucial role in the treatment of AD. RIPK1, a receptor-interacting serine/threonine-protein kinase 1, was reported to be involved in the mediation of neuronal necroptosis and neuroinflammation. Previous investigations indicated that the agonists of glucagon like peptide-1 receptor (GLP-1R) such as Liraglutide, showed ameliorating effect against the development of Alzheimer’s disease on model mice, however, the mechanisms by which GLP-1R agonists function in AD remains elusive. The effect of Liraglutide on the retardation of the AD progression upon regulation of RIPK1 was studied using biochemical and immune-histochemical assays in model mice. Results in this study ascertained that the GLP-1R agonists possessed inhibitory effect on RIPK1-mediated necroptosis and microglial activation in vitro and in vivo. It was evidenced that the utility of GLP-1R agonist is capable to reduce RIPK1 activity significantly and the effect of GLP-1R agonist showed PKA depended manner. This study clarified the relationship of GLP-1R agonist and RIPK1 and demonstrating the physiological effect of GLP-1R agonist in amelioration of AD. This study provided a mechanism underlying the function of GLP-1R agonist in AD and suggested a potential therapeutic strategies for the treatment of AD.

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Data Availability

The datasets used and / or analyzed during the current study are available from the corresponding author on reasonable request.

Change history

Abbreviations

AD:

Alzheimer’s disease

RIPK1:

Receptor-interacting serine/threonine-protein kinase 1

GLP-1R:

Glucagon-like peptide-1 receptor

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Funding

This study was supported by the National Natural Science Funding (81771221, 81870967, 81974521, 81974521 and 82071384). This study was also supported by the Tianjin health and Health Committee Foundation (ZC20184).

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Authors and Affiliations

  1. Department of Geriatrics, Tianjin Geriatrics Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China

    Xiaodong Kong

  2. Department of Pharmacy, Tianjin Medical University, Tianjin, China

    Yuting Yang, Huijie Li, Xiaohui Wu & Min Gong

  3. Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China

    Weiyun Cui, Min Gong & Ying Li

  4. WIMM, University of Oxford, Oxford, UK

    Min Gong

Authors
  1. Xiaodong Kong
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  2. Yuting Yang
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  3. Huijie Li
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  4. Weiyun Cui
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  5. Xiaohui Wu
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  6. Min Gong
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  7. Ying Li
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Corresponding authors

Correspondence to Min Gong or Ying Li.

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The authors declare that they have no Conflict of interest.

Ethical approval

All animal experiments were approved by the General Hospital of Tianjin Medical University and performed following the Guide for the Care and Use of Laboratory Animals and Stroke Treatment.

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The original online version of this article was revised: the affiliation of Xiaodong Kong has been corrected.

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Kong, X., Yang, Y., Li, H. et al. GLP-1 Receptor Agonist Inhibited the Activation of RIPK1 for Alleviation the Neuronal Death and Neuroinflammation in APP/PS1 Mice. Int J Pept Res Ther 27, 1699–1707 (2021). https://doi.org/10.1007/s10989-021-10202-2

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  • DOI: https://doi.org/10.1007/s10989-021-10202-2

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