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

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.